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HpB Cancer Regimens v.5.2 NWLCN 20 Oct 2011

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1. Neutrophils Platelets X109 L x10 L gt 1 5 and gt 100 Full dose lt 1 5 or lt 100 Do not give Discuss with consultant Diarrhoea gt Grade 2 5FU 25 dose reduction Proteinuria Streptozocin Consider dose reduction or stopping streptozocin Renal impairment DI Oncol Handbook 2004 gt 50ml min 10 49mls min lt 10ml min Full dose Streptozocin 25 dose reduction Discuss with consultant Streptozocin 50 dose reduction 18 Strep 5FU 5 day CTIS 1222 Strepozocin 5 Fluorouracil Interval between cycles Number of cycles Test to OK Confirm each cycle of chemo Supportive drugs with each cycle Patient information 500mg m 400mg m IV over 4 hours IV over 1hour Days 1to5 Days 1 to 5 Repeat every 4 5 weeks Neuroendocrine tumours Tests before starting course of chemo 4 cycles and reassess FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis tumour markers as indicated in table on page 3 FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis with every 5 week cycle Dipstick for proteinuria with every cycle High risk antiemetics as per NWLCN guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN HpB Cancer Regimens Oct 2011 12 doc HPB page 34 of 58 19 20 Macmillan drug specific information sheet
2. Side effect Strep MdG Dose Modification Source Focus CR08 Trial 2000 Haematology CR08 Neutrophils x10 L 21 5 and gt 100 lt 1 5 or lt 100 Platelets x10 L Full dose Do not give Discuss with consultant Renal function DI Oncol Handbook 2004 250mls min 10 49mls min lt 10mls min Full dose Streptozocin 25 dose reduction Discuss with consultant Consider streptozocin 50 dose reduction 5FU guidance unclear Hepatic function Unclear guidance Discuss with consultant Stomatitis Focus If mouth ulcers occur despite routine chlorhexidine mouthwash SFU 20 dose reduction bolus and infusion Continue with this reduced dose unless further toxicity occurs Diarrhoea Focus Between cycles treat symptomatically Loperamide 2 4mg QDS PRN and or codeine phosphate 30 60mg QDS PRN Not resolved by next cycle Delay 1 week until recovered If diarrhoea still a problem e Despite symptomatic treatment e Ormore than one delay is required Then dose reduce 5FU 20 dose reduction bolus and infusion Continue with this reduced dose unless further toxicity occurs Hand Foot Syndrome 2Grade 2 Stop 5FU until recovery then restart with 5FU 20 dose reduction bolus and infusion for subsequent cycles Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended Pro
3. 2 appearance 3 appearance Interrupt capecitabine until resolved to grade 0 to 1 Interrupt capecitabine until resolved to grade 0 to 1 Discontinue capecitabine treatment permanently Capecitabine 25 dose reduction Capecitabine 50 dose reduction Do not give Grade 4 1 appearance Discontinue permanently If consultant considers it is in best interest of patient to continue interrupt capecitabine until resolved to grade 0 to 1 Discontinue permanently If consultant considers it is in best interest of patient to continue then Capecitabine 50 dose reduction HpB Cancer Regimens Oct 2011 12 doc HPB page 58 of 58
4. Focus 2 SPC 250mls min 40 49mls min 30 39mls min lt 30mls min Full dose Full dose Full dose Full dose Capecitabine SPC Full dose recommends no dose adjustment of starting dose for 1250mg m day but recommends careful monitoring and prompt treatment interruption if patient develops a grade 2 3 or 4 adverse event and dose adjustments as per SPC table on page 21 25 dose reduction Full dose Discuss with Full dose consultant Do not give EOX Do not give EOX Do not give EOX Cardiotoxicity REAL 2 Unexplained cardiac failure Any patient who develops unexplained cardiac failure while on treatment should undergo evaluation of cardiac function with a MUGA scan or echocardiogram If left ventricular function is less than the lower limit of normal range then epirubicin should be omitted Stomatitis SPC REAL 2 Grade 1 gt Grade 2 Recurrent Grade 3 Consider topical treatments eg Difflam mouthwash or sucralfate mouthwash 19 5mls QDS As Grade 1 plus stop capecitabine until recovery then restart with dose according to SPC table page 20 As Grade 2 but if Grade 3 4 stomatitis recurs despite HpB Cancer Regimens Oct 2011 12 doc HPB page 44 of 58 Side effects EOX Dose Modifications Source REAL 2 appropriate capecitabine dose reduction then reduce oxaliplatin doses to 100mg m in subsequent cycles Diarrhoea REAL 2 SPC lt Grade 1 gt Grade 2 Recurre
5. 16 tal J Clin Oncol 1997 15 808 15 1998 9 4 47 Seymour MT et al HPB page 15 of 58 Table DeGramont Modified Cisplatin NB Palliative patients will require greater dose reductions than stated below based on individual patient parameters Discuss with consultant Side Effect MdG Cisplatin Dose Modification Source Focus CR08 Trial 2000 Haematology CR08 Neutrophils Platelets x10 L x10 L gt 1 5 and gt 100 lt 1 5 or lt 100 Full dose Delay until recovery Only treat when WBC neutrophils and platelets are above these limits If more than 1 delay or one delay of 42 weeks occurs then restart with 5FU 20 dose reduction bolus and infusion Continue with this reduced dose unless further toxicity occurs If further delays for myelotoxicity occur despite the 20 dose reduction discuss with consultant Renal function Crcl Cisplatin standardised Mar 09 based on ABC02 2 gt 60mls 50 59mls min 40 49mls min 30 39mls min lt 30mls min All drugs full dose Cisplatin 25 dose reduction 5FU Full dose Cisplatin 50 dose reduction 5FU Full dose Cisplatin Do not give Discuss carboplatin with consultant 5FU Full dose Discuss with consultant Hepatic function Unclear guidance Discuss with consultant Stomatitis Focus If mouth ulcers occur despite routine chlorhexidine mouthwash SFU 20 dose reduction bolus and infusion Continue with this reduce
6. 78 1450 3 2 1 79 1 92 1500 3 1 93 2 06 1650 1 3 2 07 2 18 1800 2 3 22 19 1800 2 3 Administer Monday to Friday only each week during the 5 weeks of radiotherapy Repeat tests every 2 3 weeks Ideally RT should be delivered within 2 hours of capecitabine dose Monday to Friday during 5 weeks of radiotherapy Tests before starting course of chemo FBC U amp Es LFTs Crcl calculated Do EDTA if lt 60mls min Tumour markers in table on page 3 Baseline ECG if history of ischaemic heart disease or cardiac risk factors Test to OK Confirm each cycle of chemo FBC and U amp Es weekly LFTs every 2 3 weeks Do EDTA if rising serum creatinine Supportive drugs with each cycle Low risk antiemetics as per NWLCN Patient information Additional information guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Chemotherapy treatment booklet local information Macmillian Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Patient must attend capecitabine radiotherapy nurse counselling for cycle 1 and 2 See page 18 Dose modifications For chemotherapy dose modifications see table Capecitabine RT below Reference IJROBP 2005 Kim JC etal HpB Cancer Regimens Oct 2011 12 doc HPB page 56 of 58 Table Capecitabine RT NB Palliative patients or radical chemo radiat
7. Cancer Regimens Oct 2011 12 doc HPB page 23 of 58 Side effect Gem1g Cisp60 Dose Modification ABC02 trial Peripheral neuropathy Grade 1 2 Cisplatin delay until recovery to baseline then continue at full dose If no recovery do not give cisplatin Gemcitabine full dose Grade 3 4 Cisplatin Do not give further cisplatin Gemcitabine Continue with full dose Oedema Dipstick urine test for protein If positive do 24 hour urinary Grade 3 4 protein estimation Delay until recovery to baseline with appropriate diuretics Then Gemcitabine 25 dose reduction If does not respond to above measures stop treatment Tinnitus Full dose all drugs If full recovery between cycles Cisplatin Do not give If no recovery between cycles Gemcitabine Full dose Gemcitabine 1 8 15 CTIS 561 Gemcitabine 1000mg m IVI over 30mins Days 1 8 15 Repeat every 28 days N B Treatment may start with weekly chemotherapy for 7 weeks i e days 1 8 15 22 29 36 43 then one week off then treatment follows day 1 8 15 repeat day 28 Interval between cycles 28 days Number of cycles Adjuvant or palliative Pancreatic cancer 6 cycles Tests before starting course of chemo FBC U amp Es LFTs Crcl calculated tumour markers indicated in table on HPB page 3 Tests to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl calculated Supportive drugs with each cycle Low risk antiemetics as per NWLCN g
8. Stop capecitabine until recovery Once recovered dose according to SPC table below Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of SFU induced hand foot syndrome Pyridoxine is not recommended DPD Deficiency Focus 1 3 of patients have markedly exaggerated capecitabine toxicity due to reduced capecitabine catabolism Discuss with consultant Cardiotoxicity Focus Uncommon Capecitabine may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non capecitabine treatment Neurotoxicity Focus Uncommon Cerebellar Consider alternative non capecitabine treatment HpB Cancer Regimens Oct 2011 12 doc HPB page 20 of 58 Capecitabine Non haematological toxicity SPC NCIC During course of treatment Dose adjustment for next cycle Grade Grade 1 Continue treatment Capecitabine full dose Grade 2 1 appearance nd 2 appearance 3 appearance 4 appearance Interrupt capecitabine until resolved to grade 0 1 Interrupt capecitabine until resolved to grade 0 1 Interrupt capecitabine until resolved to grade 0 1 Discontinue capecitabine permanently Capecitabine full dose Capecitabine 25 dose reduction Capecitabine 50 dose reduction Stop treatment Grade 3 1 appearance 2 appearance 3 ap
9. cycles Repeat day 7 ie Given weekly during course of radiotherapy Number of cycles Pancreatic cancer 1st line in accordance with NICE guidance but at a reduced dose during course of radiotherapy usually weekly for 5 weeks Tests before starting course of chemo FBC U amp Es LFTs tumour markers indicated in table on page 3 Tests to OK confirm each cycle of chemo FBC U amp Es LFTs Supportive drugs with each cycle Low risk antiemetics as per NWLCN guidelines or as per local policy Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information See Gemcitabine administration notes page 22 Dose modifications See table page 25 Reference HpB Cancer Regimens Oct 2011 12 doc HPB page 55 of 58 32 Capecitabine 1650 RT CTIS 1028 Capecitabine 825mg m Oral twice a day Days 1 to 5 ie total 1650mg m day See dose table below Interval between cycles Number of cycles Body Surface Dose 825mg m Twice a day Area Dose per Number of 150mg and or 500mg tablets per m Administration administration Each administration to be mg given morning and evening 150mg 500mg 1 26 1000 2 1 27 1 29 1000 2 1 30 1 49 1150 1 2 1 50 1 66 1300 2 2 1 67 1
10. leucopenia grade 4 occurs SPC July 02 or if more than 1 delay or 1 delay greater than 2 weeks Myelotoxicity more common than with Degramont alone Full dose Delay 1 week and recheck FBC Only give when neutrophils and platelets are above these limits Irinotecan 20 dose reduction SFU bolus and infusion 20 dose reduction If further delays occur for myelotoxicity despite 20 reduction discuss with consultant Renal function Crcl lt 50mls min Unclear guidance Discuss with consultant Hepatic Function SPc lrinotecan and metabolites cleared by biliary excretion Delayed clearance in cholestasis Bilirubin ALP lt 1 5 x ULN and 5 0 x ULN Full dose all drugs 1 5 3 0 x ULN or gt 5 0 x ULN Irinotecan 50 dose reduction 5 Fluorouracil Full dose gt 3 x ULN and Any Irinotecan Do not give 5 Fluorouracil 50 dose reduction Stomatitis Focus Routine mouth care with chlorhexidine mouthwash If mouth ulcers occur despite this dose reduce SFU 20 dose reduction bolus and infusion for all subsequent cycles Diarrhoea Immediate diarrhoea within first 24 hours Delayed diarrhoea occurring more than 24 hours after irinotecan and at any time before next cycle Initial treatment Lasts gt 24 hours Lasts gt 48 hours Incidence of immediate diarrhoea is low due to use of atropine premed If acute diarrhoea cholinergic syndrome occurs administer another dose of
11. loperamide 2 4mg QDS prn oral max 16mg 24hrs or codeine phosphate 30 60mg oral QDS As grade 1 plus stop 5FU until recovery Restart at 150mg m day or 50mg m day reduction As grade 1 plus stop 5FU until recovery Restart at 100mg m day or 100mg m day reduction As grade 1 plus stop 5FU until recovery Restart at 50mg m day Hand Foot Syndrome Real 2 Grade 1 Grade 2 Grade 3 Grade 4 5FU full dose Stop 5FU until recovery Restart at 150mg m day or 50mg m day reduction Stop 5FU until recovery Restart at 100mg m day or 100mg m day reduction As grade 1 plus stop 5FU until recovery Restart at 50mg m7 day Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended DPD Deficiency 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU catabolism Discuss with consultant Cardiotoxicity Uncommon 5FU may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on HpB Cancer Regimens Oct 2011 12 doc HPB page 14 of 58 Side Effect CISP60 5FU Contin Dose Modification Real 2 upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment Neurotoxicity gt Grade 2 or new functional Stop cisplatin deterioration in hearing new tinnitus or Consider alte
12. then repeat weekly for 4 Then 3 4 weeks no treatment restart week 9 10 Do not reload after cycle 1 Subsequent cycles no loading weekly chemo for 5 weeks 3 4 weeks no treatment restart week 9 10 Number of cycles 1 line relapse Tests before starting course of chemo Test to OK Confirm each cycle of chemo HpB Cancer Regimens Oct 2011 12 doc Neuroendocrine tumours 4 cycles then reassess Can be repeated FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis tumour markers as indicated in table on page 3 FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis with every 5 HPB page 33 of 58 Supportive drugs with each cycle Patient information week cycle Dipstick for proteinuria with every weekly cycle Review treatment if proteinuria High risk antiemetics as per NWLCN guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN If borderline proteinuria patient may need to do dipstick for urine analysis at home Additional information Dose modifications Reference Table Strep 5FU Streptozocin painful if given too quickly See table Strep 5FU below Dose Modification Dr Wasan Side effect Strep 5FU Haematology
13. up to 2 cycles Check with consultant Atropine 250mcg SC bolus dose Day 1 lrinotecan 100mg m IV over 30 mins Day 1 Folinic acid 350mg IV over 2 hours Day 1 5Fluorouracil 400mg m IV bolus dose Day 1 5Fluorouracil 2400mg m IV over 46hours Day 1 Interval between cycles Number of cycles HpB Cancer Regimens Oct 2011 12 doc Repeat every 14 days as detailed above For additional private care only pending review by London HPB page 51 of 58 Cancer Drugs Fund Only for loco regional treatment of HCC confined to liver Hepatocellular carcinoma with Childs Pugh A or possible good B 1 cycle of radioembolisation Tests before starting course of chemo e Preliminary arteriogram of liver within 32 days of RE to determine vascular anatomy of the liver to provide road map of arterial supply of liver to plan delivery of SIR spheres see User manual e Break through macro aggregated albumin MAA nuclear scan within 32 days of RE to calculate percentage of SIR spheres that will pass through the liver and lodge in lungs due to arteriovenous shunts Dose must be adjusted to limit y damage to lung see SIR spheres User manual e Contrast enhanced helical CT scan to calculate tumour involvement needed to calculate SIR sphere dose see SIR sphere users manual FBC U amp Es LFTs Crcl calculated Do EDTA if lt 60mls min INR tumour markers in table on page 3 Childs Pugh score Tests to OK confirm each cycle of che
14. x10 L x10 L 21 5 and gt 100 Full dose lt 1 5 or lt 100 Do not give Discuss with consultant Hepatic Function HEP 1 Bilirubin lt 18 micromol L Full dose 18 50 micromol L Doxorubicin epirubicin 50 dose reduction gt 50 micromol L Do not give 24 Epirubicin 50 Systemic CTIS 1743 Epirubicin 50mg m IV bolus Day 1 Interval between cycles Repeat every 21 days Number of cycles Hepatocellular carcinoma with Childs Pugh A or possibly good B 4 6 cycles Tests before starting course of chemo FBC U amp Es LFTs tumour markers indicated in table on page 1 INR Childs Pugh score cardiac assessment Check lifetime Cumulative epirubicin dose does not exceed 900mg m lifetime Tests to OK Confirm chemo FBC U amp Es LFTs Childs Pugh score Supportive drugs with each cycle High risk antiemetics as per NWLCN guidelines or as per local policy Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional nursing information Consider cold cap See Doxorubin page 39 Dose modifications see Doxorubicin epirubicin table above Reference Chemo Embolisation 25 Cisplatin Chemoembolisation CTIS 1744 This is only indicated if approved by the Liver MDT and there is no evidence of port
15. 3 infection fever with Full dose on Full dose on Epirubicin 25 neutropenia ANC lt 1 at any time subsequent subsequent dose reduction on cycles cycles subsequent cycles Grade 4 infection fever with Full dose on Full dose on Epirubicin 50 neutropenia ANC lt 1 at any time subsequent subsequent dose reduction on cycles cycles subsequent cycles HpB Cancer Regimens Oct 2011 12 doc HPB page 11 of 58 Side effect ECF Dose Modification Source REAL 2 Trial Renal Function Cisplatin 5FU Epirubicin Cisplatin standardised Mar 09 based on ABC02 Crcl EDTA 260mls min Full dose Full dose Full dose 50 59mls min 25 dose Full dose Full dose reduction 40 49mls min 50 dose Full dose Full dose reduction 30 39mls min Do not give Full dose Full dose Discuss carboplatin with consultant lt 30mls min Do not give Discuss with Discuss with consultant consultant Hepatic Function Real 2 Bilirubin gt 1 5 x ULN Omit epirubicin until bilirubin returns to below this level Transaminases ref 1 2xULN Consider epirubicin dose reduction Discuss with consultant Stomatitis Real 2 Grade 1 Consider topical treatments eg Difflam mouthwash or sucralfate 1g 5mls mouthwash QDS Grade 2 As grade 1 plus stop 5FU until recovery Restart at 150mg m day or 50mg m day reduction Grade 3 As grade 1 plus stop 5FU until recovery Restart at 100mg m7 day or 100mg m day re
16. D Deficiency 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU catabolism Discuss with consultant Cardiotoxicity Uncommon 5FU may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment Neurotoxicity Uncommon Cerebellar Consider alternative non 5FU treatment HpB Cancer Regimens Oct 2011 12 doc HPB page 6 of 58 3 MAYO Adaptations 5FU425 FA20 5 day CTIS 739 or 5FU 370 FA20 5day CTIS 659 Folinic Acid 20mg m IV bolus Days 1 to 5 5 Fluorouracil dose determined by age see below Dose under 70 years And ECOG lt 1 425mg m IV bolus Days 1 to 5 Dose over 70 years and or ECOG 22 370mg m IV bolus Days 1 to 5 Interval between cycles Repeat every 28 days Number of cycles HPB 6 cycles 6 months Tests before starting course of chemo Tests to OK Confirm each cycle of chemo Supportive drugs with each cycle Patient information FBC U amp Es LFTs tumour markers indicated in table on page 3 INR if hepatocellular cancer FBC U amp Es LFTs INR if hepatocellular cancer Low risk antiemetics as per NWLCN guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Loperamide 2 4mg QDS PRN max 16mg day Ice chips 5 minutes before and for 30 minutes after injection if tolerated to reduce mucositis Focus Ch
17. NHS North West London Cancer Network HEPATO PANCREATICO BILIARY Including Neuroendocrine and GISTs Section by Dr Harpreet Wasan Dr Rohini Sharma and Dr Alexandra Taylor Version HPB Regimens v5 2 NWLCN 200ct11 Section last updated 19 September 2011 Section last corrected 20 October 2011 Approved by GI Oncology Lead Clinician Dr H Wasan Date Approved by NWLCN HPB Tumour Group Professor N Habib Date Review Date September 2012 INDEX Page Tumour Markers 3 CHEMOTHERAPY ALONE 9 Fluorouracil Single Agent 1 Degramont CTIS 734 CVAD 3 CTIS 1219 NS 3 2 Lokich 5FU 300 Contin CTIS 221 5 3 Mayo CTIS 739 659 7 9 Fluorouracil Cisplatin Combination 4 ECF CTIS 270 10 5 CF Cisp60 5FU Contin CTIS 1221 13 6 MdG Cisp60 Modified Degramont Cisplatin CTIS 1751 15 Capecitabine Combinations 7 ECX CTIS 1027 17 8 CX Cisplat 60 Cape1250 CTIS 1707 21 Gemcitabine Regimens 9 Gemcitabine 1g Cisplatin 60 CTIS 563 22 10 Gemcitabine 1g Cisplatin 25 split dose ABCO2 CTIS 1734 22 11 Gemcitabine 1 8 15 CTIS 561 24 Targeted Therapies 12 Imatinib CTIS 1035 25 13 Sorafenib Cancer Drugs Fund CTIS 1735 26 14 Sunitinib 50 break SPC Cancer Drugs Fund CTIS 1737 28 15 Sunitinib 37 5 continuous Cancer Drugs Fund CTIS 1736 31 16 Everolimus Cancer Drugs Fund CTIS 1738 31 HpB Cancer Regimens Oct 2011 12 doc HPB page 1 of 58 Streptozocin Regimens 17 Streptozocin 5FU weekly Loading Maintenance 18 Streptozocin 5FU 5day 19 Streptozoci
18. abnormal ECG should have pre treatment evaluation of cardiac function with MUGA scan or equivalent If left ventricular ejection fraction is less than 50 prior to treatment then omit epirubicin MAGIC Tests to OK Confirm each cycle of chemo FBC U amp Es Mg LFTs Crcl calculated Do EDTA if rising serum creatinine Supportive drugs with each cycle Very high risk antiemetics as per NWLCN guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Loperamide 2 4mg QDS orally PRN max 16mg 24hours Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Administration notes Epirubicin Vesicant administer according to WLCN protocol Cisplatin Weigh patient before and after cisplatin infusion or monitor urine output If weight gain gt 1 5kg or symptomatic of fluid retention inform doctor patient may require diuretics Inpatients should be on a fluid balance chart and weighed daily Average urine output of at least 100ml hr is expected during and for 6 hours after cisplatin infusion Outpatients should be encouraged to drink 3 litres of fluid within the following 24 hours 5 Fluorouracil If 5FU administered using an ambulatory infusion pump via a central venous access devi
19. al venous involvement Fluids only for 3 hours before procedure Day 1 Prophylactic antibiotics 1 hour before procedure Day 1 Selective cannulation of hepatic artery arteries supplying the tumour Day 1 Then Cisplatin 50mg flat dose mixed by radiologist and given Intra arterially Day 1 Lipiodol 4 10mls Followed by Embolisation with PVA particles gt 300microns Intra arterially Day 1 any component may be omitted if clinically indicated Antibiotics post procedure Interval between cycles 6 10 weeks if patient shows no persistent ill effects Number of cycles Only for loco regional treatment of HCC confined to the liver HpB Cancer Regimens Oct 2011 12 doc HPB page 40 of 58 Hepatocellular carcinoma with Childs Pugh A or possibly good B Aim for 2 cycles If tolerated may be repeated beyond 2 cycles in selective good responders Tests before starting course of chemo Preliminary hepatic artery angiography under local anaesthetic sedation analgesia to map out anatomy of hepatic arteries and confirm patency of portal vein FBC U amp Es LFTs INR Crcl calculated do EDTA if lt 6O0mls min tumour site markers in table on page 3 Childs Pugh score cardiac assessment Tests before each cycle FBC U amp Es LFTs INR Childs Pugh score Supportive drugs with each cycle Fluids only 3 hours before procedure Prophylactic antibiotics 1 hour pre procedure Lipiodol as above Emboli PVA as above Prophylactic antibiotics
20. ally Avoid alcohol and peroxide containing mouthwashes Only use antifungal agents if fungal infection diagnosed Blood Glucose and Lipids Hyperglycaemia Hyperlipidaemia Hypertriglyceridaemia Monitor and institute therapy to correct abnormalities Hyperglycaemia prior to treatment commencing should be corrected if possible before starting everolimus Interactions Co administration with inhibitors and inducers of CYP3A4 and or the multidrug efflux pump P glycoprotein PgP should be avoided See SPC for guidance Wound Healing Everolimus is associated with impaired wound healing Care should be exercised in pre surgical patients or patients with other wounds Streptozocin Regimens There is a world wide shortage of streptozocin 2009 Contact pharmacy to secure supplies DO NOT consent new patients until pharmacy has confirmed supplies have been secured for the whole course for the new patient Decision to prescribe streptozocin must be discussed at MDT 17 Cycle 1 Streptozocin 1000mg m 5Fluorouracil 1000mg m Subsequent cycles 3 4 week interval Streptozocin 1000mg m 5Fluorouracil 1000mg m Interval between cycles further weeks STZ 5FU Cycle 1 Day1 2 loading CTIS 1228 maintenance CTIS 1225 IV over 4 hours IV over 1 hour Day 1 2 8 15 22 29 Day 1 2 8 15 22 29 IV over 4 hours IV over 1 hour Day 1 8 15 22 29 Day 1 8 15 22 29 Cycle 1 Loading dose days 1 and 2
21. as appropriate HpB Cancer Regimens Oct 2011 12 doc HPB page 3 of 58 Neutropenia DVD NWLCN Additional information DeGramont Regimens May 2005 all DeGramont regimens for upper GI standardised to the modified version either via a CVAD infusor or via peripheral line litre infusion bags Administration notes If 5FU administered using an ambulatory infusion pump via a central venous access device CVAD refer to relevant protocol for care of CVAD Joint care with the community nursing services should be arranged in advance to support the patient and to assist with disconnecting the chemotherapy and flushing the CVAD Written community nursing referral should be completed and the patient should be discharged with a home spillage kit sharps container and a small supply of equipment to flush the line and dress the entry site of the CVAD Dose modifications See DeGramont modified table below References DeGramont et al J Clin Oncol 1997 15 808 15 Annals Oncol 1998 9 4 47 Seymour MT et al Table DeGramont Modified NB Palliative patients will require greater dose reductions than stated below based on individual patient parameters Discuss with consultant Side Effect MdG Dose Modification Source Focus CR08 Trial 2000 Haematology CR08 Neutrophils Platelets x10 L x10 L 21 5 and gt 100 Full dose lt 1 5 or lt 100 Delay until recovery Only treat when neutrophils and platelets are above these lim
22. atropine 250mcg SC stat lrinotecan induced delayed diarrhoea should be treated early with high dose loperamide 4mg after first loose stool then 2mg every 2 hours until 12 hours after last loose stool up to 24mg day for a maximum of 48 hours because or risk of paralytic ileus If diarrhoea lasts gt 24 hours add Ciprofloxacin PO 500mg BD If diarrhoea lasts gt 48 hours or patient reports symptoms of dehydration admit acutely for rehydration HpB Cancer Regimens Oct 2011 12 doc HPB page 53 of 58 Side Effect IrMdG Dose Modification Source Focus Trial SPC Grade 3 4 Unresolved by next cycle and further management After an episode of severe diarrhoea grade 3 4 delay until full recovery then resume at lrinotecan 20 dose reduction 5FU bolus amp infusion 20 dose reduction If diarrhoea from previous cycle even if not severe not resolved by next cycle due delay 1 week Hand Foot Syndrome gt Grade 2 SFU 20 dose reduction bolus and infusion lrinotecan full dose Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended DPD Deficiency Focus 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU catabolism Discuss with consultant Cardiotoxicity Focus Uncommon 5FU may provoke angina attack or MI in patients with ischaemic heart
23. blem reduce dose according to table page 8 Hand and Foot Syndrome Reduce dose according to table page 8 Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended DPD Deficiency Focus 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU catabolism Discuss with consultant Cardiotoxicity FOCUS Uncommon 5FU may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment Neurotoxicity Focus Uncommon Cerebellar Consider alternative non 5FU treatment HpB Cancer Regimens Oct 2011 12 doc HPB page 9 of 58 5 Fluorouracil Cisplatin Combination Chemotherapy 4 ECF via CVAD CTIS 270 Epirubicin 50mg m IV bolus Day 1 Prehydrations Day 1 Cisplatin 60mg m IV over 2 hours Day 1 Post hydrations Day 1 5 Fluorouracil 200mg m day IV continuous infusion Days 1 to 21 starting 4 hours before cisplatin on first cycle Interval between cycles Repeat every 21 days Number of cycles HPB Metastatic palliative 4 8 cycles Tests before starting course of chemo FBC U amp Es Mg LFTs Crcl calculated Do EDTA if lt 60mls min tumour markers in table on Page 3 Cardiac assessment patients with a history of ischaemic heart disease and
24. cal haematological ee a ee es recovery then recovery then and non neutrophils 1 0 eae provided give full dose give 20 dose haematological platelets 2100 reduction recovery to toxicity grade lt 2 then give 50 dose reduction 0 5 0 99 Or 25 49 Delay until full Delay until Delay until full Do not give haematological haematological haematological recovery then recovery then and non give 20 dose give 30 dose haematological reduction reduction recovery to toxicity lt grade 2 then give 50 dose reduction lt 0 5 Or lt 25 Delay until Delay until Delay until full Do not give haematological recovery then give 50 dose reduction haematological recovery then give 50 dose reduction haematological and non haematological recovery to toxicity lt grade 2 then give 50 dose reduction Do not dose reduce Folinic Acid HpB Cancer Regimens Oct 2011 12 doc HPB page 8 of 58 Side Effect MAYO Haematology Dose Modification Source Quasar FOCUS trials See table above Renal function GFR below 30ml min Unclear guidance Discuss with consultant Hepatic function Unclear guidance Discuss with consultant Stomatitis Routine mouthcare with chlorhexidine Ensure ice chips are being used If still a problem reduce dose according to table page 8 Diarrhoea Give loperamide 2 4mg oral QDS PRN max 16mg 24hours or codeine phosphate 30 60mg oral QDS PRN If still a pro
25. ce CVAD refer to relevant protocol for care of CVAD Joint care with the community nursing services should be arranged in advance to support the patient and to assist with disconnecting the chemotherapy and flushing the CVAD Written community nursing referrals should be completed and the patient should be discharged with a home spillage kit sharps container and a small supply of equipment to flush the line and dress the entry site of the CVAD HpB Cancer Regimens Oct 2011 12 doc HPB page 10 of 58 Dose modifications Table ECF below Reference Br J Cancer 1999 80 269 72 Waters et al EJC 2003 1 5 suppl Cunningham et al Table ECF NB Palliative patients will require greater dose reductions than above based on individual patient parameters Discuss with consultant Side effect ECF Dose Modification Source REAL 2 Trial Haematology REAL 2 Cisplatin 5FU Epirubicin Neutrophils Platelets x 10 L x 10 L gt 1 0 and gt 75 Full dose Full dose Full dose 0 5 0 9 or 50 74 Delay until Stop 5FU until Delay until recovery then full recovery then full recovery then dose dose give epirubicin 25 dose reduction lt 0 5 or 25 49 Delay until Stop 5FU until Delay until recovery then full recovery then full recovery then dose dose give epirubicin 50 dose reduction Any or lt 25 Delay until Stop 5FU until Omit on recovery then full recovery then full subsequent dose dose cycles Neutropenic fever REAL 2 Grade
26. cin 75 dose reduction Do not give Doxorubicin 25 dose reduction Anthracycline Regimens 23 Doxorubicin 75 Systemic CTIS 1742 Doxorubicin 75mg m IV bolus Day 1 Interval between cycles Repeat every 21 days Number of cycles Hepatocellular carcinoma with Childs Pugh A or possibly good B 4 6 cycles Tests before starting course of chemo Test to OK Confirm each cycle of chemo Supportive drugs with each cycle Patient information FBC U amp Es LFTs INR tumour markers indicated in table on page 3 Childs Pugh score cardiac assessment Check lifetime cumulative doxorubicin dose does not exceed 450mg m lifetime FBC U amp Es LFTs INR Childs Pugh score High risk antiemetics as per NWLCN guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Administration notes Consider cold cap Doxorubicin is a vesicant and must be administered according to WLCN administration policy Dose modifications Reference Table Doxorubicin Epirubicin See table page 40 HpB Cancer Regimens Oct 2011 12 doc HPB page 39 of 58 Side effect Dox Epi Dose Modification HEP 1 Haematology HEP 1 Neutrophils Platelets
27. cles Tests before starting course of chemo FBC U amp Es LFTs Crcl calculated tumour markers indicated in table on page 3 Cardiac assessment patients with a history of ischaemic heart disease and abnormal ECG should have pre treatment evaluation of cardiac function with MUGA scan or equivalent If left ventricular ejection fraction is less than 50 prior to treatment then omit epirubicin Tests to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl calculated Supportive drugs with each cycle High antiemetics as per NWLCN guidelines Patient information HpB Cancer Regimens Oct 2011 12 doc or as per local policy Chlorhexidine mouthwash 10mls QDS Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN HPB page 42 of 58 Additional information Administration notes Capecitabine Patients must attend a nurse capecitabine clinic prior to cycles 1 and 2 or specialist chemotherapy nurse review as per local policy Capecitabine tablets should be taken with water 30 minutes after food and approximately 12 hours apart Patients must be given written and verbal information on capecitabine including how to take the tablets when to stop ie In the event of toxicity and after 14 days and whom to contact when side effects occur Wri
28. d dose unless further toxicity occurs Diarrhoea Focus Between cycles treat symptomatically loperamide 2 4mg QDS PRN and or codeine phosphate 30 60mg QDS PRN Not resolved by next cycle Delay 1 week until recovered If diarrhoea still a problem e Despite symptomatic treatment e Ormore than one delay is required Then dose reduce 5FU 20 dose reduction bolus and infusion Continue with this reduced dose unless further toxicity occurs Hand Foot Syndrome 2Grade 2 Stop 5FU until recovered then restart with 5FU dose reduced by 20 bolus and infusion for subsequent cycles Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended HpB Cancer Regimens Oct 2011 12 doc HPB page 16 of 58 Side Effect MdG Cisplatin Dose Modification Source Focus CR08 Trial 2000 DPD Deficiency Focus 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU catabolism Discuss with consultant Cardiotoxicity Focus Uncommon 5FU may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment Neurotoxicity Focus Uncommon Cerebellar Consider alternative non 5FU treatment Capecitabine Combinations Capecitabine
29. disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment Neurotoxicity Focus Uncommon Cerebellar Consider alternative Non 5FU treatment HpB Cancer Regimens Oct 2011 12 doc HPB page 54 of 58 Chemo Radiation Regimens 30 31 5FU320 FA20 5 days plus Radiothera CTIS 204 Folinic Acid 20mg m IV bolus Days 1to5 and Days 15 19 5 Fluorouracil 320mg m IV bolus Days 1to5 and Days 15 19 Interval between cycles Single course no repeats Chemotherapy administered weeks 1 and 3 of a four week course of radiotherapy Number of cycles Pancreatic cancer Single course based on ESPACI data selected patients only Tests before starting course of chemo FBC U amp Es LFTs Crcl calculated tumour markers indicated in table on HPB page 3 Tests to OK confirm each cycle of chemo FBC U amp Es LFTs Supportive drugs with each cycle Low risk antiemetics Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Dose modifications See MAYO page 8 9 Reference Gemcitabine 300 RT CTIS 1260 Gemcitabine 300mg m IV over 30 minutes Day 1 2 hours before radiotherapy fraction Interval between
30. duction Grade 4 As grade 1 plus stop 5FU until recovery Restart at 50mg m day Diarrhoea Real 2 Grade 1 Commence loperamide 2 4mg QDS prn oral max 16mg 24hrs or codeine phosphate 30 60mg oral QDS Grade 2 As grade 1 plus stop 5FU until recovery Restart at 150mg m7 day or 50mg m day reduction Grade 3 As grade 1 plus stop 5FU until recovery Restart at 100mg m day or 100mg m day reduction Grade 4 As grade 1 plus stop 5FU until recovery Restart at 50mg m day Hand Foot Syndrome Grade 1 Full dose 5FU Grade 2 Stop 5FU until recovery Restart at 150mg m7 day or 50mg m day reduction Grade 3 Stop 5FU until recovery Restart at 100mg m day or 100mg m day reduction Grade 4 Stop 5FU until recovery Restart at 50mg m day Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended HpB Cancer Regimens Oct 2011 12 doc HPB page 12 of 58 Side effect ECF Dose Modification Source REAL 2 Trial Neurotoxicity Real 2 gt Grade 2 CTC neurotoxicity or new functional deterioration in hearing new tinnitus or significant high frequency hearing loss on audiogram Stop cisplatin Consider carboplatin AUC5 instead Cardiotoxicity Real 2 Any patient who develops unexplained cardiac failure while on treatment should undergo evaluation of cardiac function with MUGA or ECG I
31. e until disease progression Tests before starting course of chemo FBC U amp Es LFTs BP dipstick protein 24 hour urine protein quantitative analysis tumour markers in table on page 3 Tests to OK confirm each cycle of chemo FBC U amp Es LFTs BP dipstick urine 24 hour urine protein quantitative analysis every 4 5 weeks thyroid function tests every 8 weeks Supportive drugs with each cycle Chlorhexidine mouthwash 10mls QDS Loperamide 2mg QDS PRN Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Administration notes SPC Sunitinib may be taken with our without food Avoid grapefruit juice CYP3AL inhibitor Nursing notes If a dose is missed the patient should not take an additional dose The patient should take the usual prescribed dose the next day Interactions See page 30 and SPC Dose modifications See page 30 16 Everolimus 10 CTIS 1738 Apply to London Cancer Drugs Fund Everolimus 10mg Oral once a day Days 1 to 28 Swallow whole with glass of water Interval between cycles Continuous treatment until progression Repeat tests every 28 days Number of cycles Apply to Cancer Drugs Fund for Unresectable or metastatic well or moderately differentiated neuroendocrine tumours of pa
32. eets and information prescriptions as appropriate Neutropenia DVD NWLCN HpB Cancer Regimens Oct 2011 12 doc HPB page 21 of 58 Additional information Administration notes See ECX page 19 Dose modifications Reference Gemcitabine Regimens 9 Cisp60 Gem 1g CTIS 563 Pre hydrations Day 1 Cisplatin 60mg m IV over 2hrs Day 1 Gemcitabine 1000mg m IV over 30mins Days 1 and 8 Post hydrations Day 1 Interval between cycles Repeat every 21 days Number of cycles Cholangiocarcinoma or Pancreas 1 line 4 8 cycles Tests before starting course of chemo FBC U amp Es LFTs Crcl calculated Do EDTA if lt 60mls min tumour markers indicated in table on page 3 Tests to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl calculated Do EDTA if rising serum creatinine Supportive drugs with each cycle Very high risk antiemetics as per NWLCN guidelines or as per local policy Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Administration notes Gemcitabine can cause pain on administration To avoid increasing haematological toxicity gemcitabine infusion time must not exceed 1 hour If pain develops T Keep gemcitabine infusion over 30 minutes and infuse 250mls sodium c
33. elow these levels Stop chemo until resolved below these levels Stop chemo until resolved below these levels Side effect Gem D1 8 15 Dose Modification ABc 02 Lethargy Grade 3 4 Consider gemcitabine 25 dose reduction If does not respond to dose reduction stop treatment Oedema Grade 3 4 Dipstick urine test for protein If positive do 24 hour urinary protein estimation Delay until recovery to baseline with appropriate diuretics Then Gemcitabine 25 dose reduction If does not respond to above measures stop treatment Targeted Therapies 12 Imatinib CTIS 1035 Imatinib must be discussed and approved by the MDT Imatinib 400mg Oral Once a day NICE guidance does NOT permit dose escalation Interval between cycles Number of cycles HpB Cancer Regimens Oct 2011 12 doc Continuous treatment Review every 28 days Kit CD117 positive metastatic inoperable GIST without evidence of progression Continue until resistance develops HPB page 25 of 58 Tests before starting course of chemo FBC U amp Es LFTs thyroid function PET scan Requires PCT approval for each patient Tests to OK Confirm each cycle of chemo FBC U amp Es LFTs weight check for fluid Supportive drugs with each cycle retention thyroid function every 6 months None Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red b
34. emotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book HpB Cancer Regimens Oct 2011 12 doc Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Administration notes Suck ice cubes or ice lollies 5 minutes before and for 30 minutes after injection if tolerated of 5FU may reduce the incidence of stomatitis Dose Modifications See MAYO table page 8 Reference J Clin Oncol 1997 15 246 250 O Connell et al HPB page 7 of 58 Table MAYO Ref QUASAR protocol UKCCCR 1998 Radical treatment only For combination of Haematological non Haematological toxicity e Wait until FULL recovery ie neutrophils gt 1 5 x10 L and platelets gt 100 x10 L and or any persistent mucositis and diarrhoea have resolved e If within 2 weeks restart chemo using dose modifications below e If FULL recovery takes more than 2 weeks discuss with consultant Haematological Non Haematological Toxicity Toxicity On day of chemo or during previous cycle Diarrhoea or mucositis Neutrophils Platelets CTC Grade x10 L x10 L 0 1 2 3 4 21 9 And 2100 Full dose Full dose Delay until recovery Do not give to toxicity lt grade 2 then give 50 dose reduction 21 0 1 5 And or 50 99 Delay until Delay until Delay until full Do not give haematological haematologi
35. ence Streptozocin Modified DeGramont Strep MdG CTIS 1739 Streptozocin 1000mg m IV over 4 hours Day 1 and 2 Folinic acid 350mg IV over 2 hours Day 1 5Fluorouracil 400mg m IV bolus Day 1 5Fluorouracil 2400mg m IV over 46 hours Day 1 Interval between cycles Repeat every 14 21 days Number of cycles Neuroendocrine tumours where intolerant of 5FU bolus or frequent attendance problematic 6 cycles Tests before starting course of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis tumour markers as indicated in table on page 3 Test to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis with every other cycle Dipstick for proteinuria with every cycle Review treatment if proteinuria Supportive drugs with each cycle High risk antiemetics as per NWLCN guidelines or as per local policy HpB Cancer Regimens Oct 2011 12 doc HPB page 35 of 58 Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN If borderline proteinuria patient may need to do dipstick urine analysis at home Additional information Dose modifications Reference Table Streptozocin MdG Streptozocin painful if given too quickly See table Strep MdG on below
36. ends to have a high fat meal Sorafenib should be taken at least 1 hour before or 2 hours after the meal Tablets should be swallowed with a glass of water Dose modifications Reference Table Sorafenib Dose levels Level 1 Sorafenib 400mg twice a day Level 2 Sorafenib 400mg Once a day Level 3 Sorafenib 400mg every two days Side effect Sorafenib Dose Modification Nexavar SPC A6181170 trial Haematology Neutrophils Platelets x10 L x10 7 L gt 1 0 and gt 50 0 5 0 9 or 25 49 lt 0 5 or lt 25 Treat on time with no change in dose Treat on time but reduce dose by one dose level Delay until neutrophils 21 0 and platelets 250 then restart but reduce dose by one level Non Haematological Toxicity except skin Grade 0 2 Grade 3 Grade 4 Treat on time with no change in dose Delay until toxicity lt grade 2 then restart but reduce one dose level Discontinue treatment Renal function SPC No dose adjustment is required in patients with mild moderate or severe renal impairment No data available in patients requiring dialysis Monitoring of fluid balance and electrolytes in patients at risk of renal dysfunction is advised Hepatic impairment SPC No dose adjustment is required in patients with Child Pugh A and B mild to moderate hepatic impairment No data available on patients with Child Pugh C severe hepatic impairment Sorafenib is mainly eliminated via the hepatic
37. er starting at 200mg BD and escalating dose if no grade 2 or 3 toxicity Interval between cycles Review repeat tests every 28 days Number of cycles Apply to London Cancer Drugs fund for funding 1 line advanced stage Hepatocellular carcinoma or Advanced hepatocellular carcinoma with underlying cirrhosis due to hepatitis C HpB Cancer Regimens Oct 2011 12 doc Continue as long as clinical benefit or until unacceptable toxicity HPB page 26 of 58 Tests before starting course of chemo Tests to OK confirm each cycle of chemo Supportive drugs with each cycle Patient information Additional information FBC U amp Es LFTs BP dipstick protein 24 hour urine protein quantitative analysis tumour markers in table on HPB page 3 Caution in patients with prior cardiac events surgery hypertension intra abdominal tumours risk of GI perforation see SPC FBC U amp Es LFTs BP dipstick urine 24 hour protein quantitative analysis every 4 5 weeks thyroid function tests every 8 weeks Chlorhexidine mouthwash 10mls QDS Loperamide 2mg QDS PRN Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Administration notes SPC Sorafenib should be administered without food or with a low or moderate fat meal If the patient int
38. estart with full dose gt Grade 2 Stop capecitabine until recovery Once recovered reduce dose according to SPC table page 58 Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended DPD Deficiency 1 3 of patients have markedly exaggerated capecitabine toxicity due to reduced capecitabine catabolism Discuss with consultant Cardiotoxicity Uncommon Capecitabine may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non capecitabine treatment Neurotoxicity Uncommon Cerebellar Consider alternative non capecitabine treatment HpB Cancer Regimens Oct 2011 12 doc HPB page 57 of 58 Capecitabine Non haematological toxicity SPC NCIC During course of treatment Dose adjustment for next cycle Grade Grade 1 Continue treatment Capecitabine full dose Grade 2 1 appearance nd 2 appearance 3 appearance 4 appearance Interrupt capecitabine until resolved to grade 0 1 Interrupt capecitabine until resolved to grade 0 1 Interrupt capecitabine until resolved to grade 0 1 Discontinue capecitabine permanently Capecitabine full dose Capecitabine 25 dose reduction Capecitabine 50 dose reduction Stop treatment Grade 3 1 appearance
39. eutropenia DVD NWLCN Interval between cycles Number of cycles Tests to OK Confirm each cycle of chemo Supportive drugs with each cycle Patient information Additional information Administration notes Dose modifications Reference See ECF page 10 See table page 14 HPB page 13 of 58 Table CISP60 5FU Contin Side Effect CISP60 5FU Contin Dose Modification Real 2 Haematology Neutrophils Platelets x10 L x10 L gt 1 0 and gt 75 Full dose Do not give below these levels Delay until recovery and discuss with consultant Renal Function Cisplatin standardised Mar 09 based on ABC02 Crcl EDTA gt 60mls min 50 59mls min 40 59mls min 30 39mls min lt 30mls min Full dose all drugs Cisplatin 25 dose reduction 5FU Full dose Cisplatin 50 dose reduction SFU Full dose Cisplatin Do not give Discuss carboplatin with consultant 5FU Full dose Do not give Discuss with consultant Stomatitis Real 2 Grade 1 Grade 2 Grade 3 Grade 4 Consider topical treatments eg Difflam mouthwash or sucralfate 1g 5mls mouthwash QDS As grade 1 plus stop SFU until recovery Restart at 150mg m day or 50mg m day reduction As grade 1 plus stop SFU until recovery Restart at 100mg m day or 100mg m day reduction As grade 1 plus stop 5FU until recovery Restart at 50mg m day Diarrhoea Real 2 Grade 1 Grade 2 Grade 3 Grade 4 Commence
40. f left ventricular function is less than lower limit of normal range then Do not give epirubicin Uncommonly 5FU may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment DPD Deficiency Focus 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU catabolism Discuss with consultant HpB Cancer Regimens Oct 2011 12 doc CF CISP60 5FU Contin CTIS 1221 Prehydrations Day 1 Cisplatin 6O0mg m IV over 2 hours Day 1 Post hydrations Day 1 5 Fluorouracil 200mg m day IV continuous infusion Days 1 to 21 starting 4 hours before cisplatin on first cycle Repeat every 21 days Upper GI Palliative ECF alternative where epirubicin contraindicated 2 6 cycles Tests before starting course of chemo FBC U amp Es Mg LFTs Crcl calculated Do EDTA if lt 60mls min tumour markers indicated in table on page 3 FBC U amp Es Mg LFTs Crcl calculated Do EDTA if rising serum creatinine Very high risk antiemetics as per NWLCN guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Loperamide 2 4mg QDS orally PRN max 16mg day Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate N
41. hloride simultaneously down the same line via a Y connector 2 If above does not resolve pain infusion time may be increased to 45 minutes after discussion with the consultant in charge 3 If above does not resolve the pain infusion time may be increased to 60minutes after discussion with consultant in charge DO NOT INCREASE INFUSION BEYOND 60 MINUTES Dose modifications Table Gem 1g Cisp 60 below Reference 10 Cisp25 Gem 1g Day 1 8 CTIS 1734 Split dose ABCO2 Prehydration Days 1 and 8 Cisplatin 25mg m IV over 1 hour Days 1 and 8 Gemcitabine 1000mg m IV over 30 mins Days 1 and 8 Post hydrations Days 1 and 8 Interval between cycles Repeat every 21 days Number of cycles Cholangiocarcinoma or Pancreas 1 line 4 8 cycles Tests before starting course of chemo FBC U amp Es LFTs Crcl calculated Do EDTA if lt 60mls min Tumour markers indicated in table on page 3 HpB Cancer Regimens Oct 2011 12 doc HPB page 22 of 58 Tests to OK Confirm each cycle of chemo Supportive drugs with each cycle Patient information Additional information Dose modifications Reference Table Gem 1g Cisp60 FBC U amp Es LFTs Crcl calculated Do EDTA if rising serum creatinine High risk antiemetics as per NWLCN guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information
42. ion patients will require greater dose reductions than above based on individual patient parameters Discuss with consultant Side effects Capecitabine RT Dose Modifications Scope SPC Haematology Neutrophils Platelets x 10 L x 10 L 21 5 and gt 100 Full dose lt 1 5 or lt 100 Delay 1 week or until recovery If gt 1 delay or 1 delay 22 weeks dose reduce Capecitabine 20 dose reduction Continue at this lower dose for subsequent cycles unless further toxicity occurs If further delay s for myelotoxicity occur despite 20 dose reduction discuss with consultant Renal function Scope Crel gt 50mls min Full dose 40 49mls min Capecitabine 25 dose reduction 30 39mls min Capecitabine 50 dose reduction lt 30mls min Do not give Hepatic function Bilirubin Either AST or ALT lt 3 x ULN and lt 2 5 x ULN Full dose gt 3 x ULN or gt 2 5 x ULN Capecitabine withhold until recovery then discuss with consultant Diarrhoea Grade 1 Loperamide 2 4mg oral QDS PRN max 16mg 24hours gt Grade 2 As grade 1 plus stop capecitabine until recovery then reduce dose according to SPC table page 58 Stomatitis SPC Grade 1 Consider topical treatments eg Difflam mouthwash or sucralfate 1g 5ml mouthwash gt Grade 2 Stop capecitabine until recovery Consider topical treatments as grade 1 and reduce dose according to SPC table page 58 Hand Foot Syndrome Grade 1 Stop capecitabine until recovery Once recovered r
43. is NOT licensed as single agent for any upper GI HPB indications but is used in combination in ECX regimen NOTE that capecitabine has both liver toxicity and liver interactions as well as being renally cleared so should be used with care in the ECX combination Capecitabine has local approval at some sites for single agent use as sensitising agent with concurrent radiotherapy See page 59 7 ECX CTIS 1027 Epirubicin 50mg m IV bolus Day 1 Prehydrations Day 1 Cisplatin 60mg m IV over 2 hours Day 1 Post hydrations Day 1 Capecitabine 625mg m Orally twice daily after Days 1 to 21 ie total 1250mg m day meals with water Capecitabine 625mg m BD Dose Table SPC Dose 625mg m BD Dose per Number of 150mg and or 500mg Body Surface Area administration tablets per administration each m mg administration to be given morning and evening 150mg 500mg lt 1 38 800 2 1 1 39 1 52 950 3 1 1 53 1 66 1000 2 1 67 1 78 1000 2 1 79 1 92 1150 1 2 1 93 2 06 1300 2 2 2 07 2 18 1300 2 2 22 19 1450 3 2 Interval between cycles Number of cycles HPB Tests before starting course of chemo HpB Cancer Regimens Oct 2011 12 doc Repeat every 21 days 4 8 cycles FBC U amp Es Mg LFTs Crcl calculated Do EDTA if lt 60mls min tumour markers in table on page 3 Cardiac assessment patients with a history of ischaemic heart disease and abnormal ECG
44. its If more than 1 delay or one delay of 32 weeks occurs then restart with 5FU 20 dose reduction bolus and infusion Continue with this reduced dose unless further toxicity occurs If further delays for myelotoxicity occur despite the 20 dose reduction discuss with consultant Renal function GFR below 30ml min Unclear guidance Discuss with consultant Hepatic function Unclear guidance Discuss with consultant Stomatitis Focus If mouth ulcers occur despite routine chlorhexidine mouthwash 5FU 20 dose reduction bolus and infusion Continue with this reduced dose unless further toxicity occurs Diarrhoea Focus Between cycles treat symptomatically loperamide 2 4mg QDS PRN and or codeine phosphate 30 60mg QDS PRN Not resolved by next cycle Delay 1 week until recovered If diarrhoea still a problem e Despite symptomatic treatment e Ormore than one delay is required Then dose reduce 5FU 20 dose reduction bolus and infusion Continue with this reduced dose unless further toxicity occurs HpB Cancer Regimens Oct 2011 12 doc HPB page 4 of 58 Side Effect MdG Dose Modification Source Focus CR08 Trial 2000 Hand Foot Syndrome Focus Focus 2 gt Grade 2 Stop 5FU until recovered then restart with 5FU 20 dose reduction bolus and infusion for subsequent cycles Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment
45. liplatin in subsequent cycles Discuss carboplatin substitution with consultant Parasthesia with pain Lasting 1 7 days Lasting gt 7 days Persistent between cycles Full dose Oxaliplatin reduce dose to 100mg m on subsequent cycles If recurs despite dose reduction omit oxaliplatin on subsequent cycles Stop oxaliplatin Discuss carboplatin substitution with consultant Paraesthesia with functional impairment Lasting 1 7 days Lasting gt 7 days Persistent between cycles Full dose Oxaliplatin reduce dose to 100mg m on subsequent cycles If recurs despite dose reduction omit oxaliplatin on subsequent cycles Stop oxaliplatin Discuss carboplatin substitution with consultant HpB Cancer Regimens Oct 2011 12 doc HPB page 45 of 58 28 Radio Embolisation Recruit to trials whenever possible Radioembolisation RE is a technique that has been developed to target multiple sites of disease within the liver as a form of bracytherapy SlR Spheres Sirtex Medical Ltd Sydney Australia contain the pure B emitter yttrium 90 labelled to resin microspheres with a mean diameter of approximately 32 um The physical half life of yttrium 90 is 64 1 hours In a single out patient procedure involving trans femoral catheterisation and fluoroscopic guidance approximately 40 to 80 million microspheres are injected into the arterial supply of the liver Hepatic metastases can derive approximately 90 of their bl
46. lt 9 Full dose Do not give until recovered to above levels Renal Function CrCl 225mls min SPC states no dose adjustment required Hepatic Function Child Pugh Class B Moderate hepatic impairment Child Pugh Class C Severe hepatic impairment Reduce dose to Everolimus 5mg once a day Not recommended Non Infectious Pneumonitis See SPC for diagnosis Radiological changes suggestive of non infection pneumonitis with few or no symptoms Radiological changes suggestive of non infectious pneumonitis with moderate symptoms Severe symptoms of non infections pneumonitis Continue without dose adjustment Discuss with consultant Consider interrupting treatment until symptoms improve Corticosteroids may be indicated If restarted give everolimus 5mg once a day Stop everolimus Corticosteroids may be indicated until clinical symptoms resolve HpB Cancer Regimens Oct 2011 12 doc HPB page 32 of 58 Side Effect Everolimus Dose Modification Discuss with consultant and if therapy to restart give everolimus 5mg once a day Opportunistic Infections Localised and or systemic infections Pre existing infections Invasive systemic fungal infection Treat promptly Treat appropriately BEFORE starting treatment Stop everolimus promptly and discontinue permanently Treat infection appropriately Oral Ulceration Mouth ulcers stomatitis and oral mucositis Treat topic
47. ment of starting dose for 1250mg m day but recommends careful monitoring and prompt treatment interruption if patient develops a grade 2 30r 4 adverse event and dose adjustments as per SPC table on page 21 Discuss with consultant Do not give Full dose Full dose Full dose Full dose Do not give HpB Cancer Regimens Oct 2011 12 doc HPB page 19 of 58 Side effects ECX Dose Modifications Source REAL 2 Hepatic function SPC Real 2 Bilirubin Either AST or ALT lt 1 5x ULN and 2 5 x ULN Full dose Full dose Full dose 1 5 3 0 x ULN and 22 5 x ULN Full dose Full dose Do not give gt 3 0x ULN and gt 2 5 x ULN Discuss with Stop capecitabine Do not give consultant Discuss with consultant Stomatitis SPC Grade 1 Consider topical treatments eg Difflam mouthwash or Grade 2 2 sucralfate mouthwash 19 5mls QDS As grade 1 plus stop capecitabine until recovery dose according to SPC table below Diarrhoea REAL 2 SPC lt Grade 1 gt Grade 2 Full dose all drugs Stop capecitabine start loperamide 2 4mg QDS oral prn max 16mg 24hrs or codeine phosphate 30 60mg QDS If diarrhoea resolves within 2 days restart all drugs full dose If diarrhoea persists wait until recovery then Capecitabine dose reduction as per SPC table below Hand Foot Syndrome SPC Grade 1 gt Grade 2 Stop capecitabine until recovery Once recovered restart full dose all drugs
48. metics as per NWLCN guidelines or as per local policy NB In cycle 2 continue 5HT3 antiemetics to cover day of RE as a minimum Chlorhexidine mouthwash 10mls QDS Loperamide 2 4mg QDS PRN max 16mg day Proton pump inhibitor from day of diagnostic hepatic arteriogram for minimum 8 weeks Fluids only 3 hours before RE Prophylactic antibiotics 1 hour before procedure according to local policy Prophylactic narcotic analgesia for RE procedure Minor opioids dihydrocodeine usually sufficient but major opioids eg pethidine may be required within first 24 hours of RE Prophylactic antibiotics post procedure according to local policy Patient Information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN SIR Sphere patient information Additional information Dose modification HpB Cancer Regimens Oct 2011 12 doc HPB page 47 of 58 Table SIR Spheres Side effect Dose Modification FOXFIRE TRIAL Fever Most patients up to 80 develop a mild fever that lasts several days following RE administration but which does not require treatment Abdominal Pain RE is followed by abdominal pain in approximately 50 of patients This can vary from minor discomfort grade 1 through to grade 3 In almost all cases it is self limiting dis
49. mo FBC U amp Es LFTs INR Childs Pugh score Supportive drugs with each cycle High risk antiemetics as per NWLCN guidelines or as per local policy NB In cycle 2 continue 5HT3 antiemetics to cover day of RE as a minimum Chlorhexidine mouthwash 10mls QDS Loperamide 2 4mg QDS PRN max 16mg day Proton pump inhibitor from day of diagnostic hepatic arteriogram for minimum 8 weeks Fluids only 3 hours before RE Prophylactic antibiotics 1 hour before procedure according to local policy Prophylactic narcotic analgesia for RE procedure Minor opioids dihydrocodeine usually sufficient but major opioids eg pethidine may be required within first 24 hours of RE Prophylactic antibiotics post procedure according to local policy Patient Information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN SIR Sphere patient information Additional information Dose modification Discuss with consultant SIR Spheres see page 48 HpB Cancer Regimens Oct 2011 12 doc HPB page 52 of 58 Table lrinotecan MdG Side Effect IrMdG Dose Modification Source Focus Trial SPC Haematological Neutrophils Platelets x10 L x10 L gt 1 5 and gt 100 lt 1 5 or lt 100 If neutropenia grade 4 or febrile neutropenia or thrombocytopenia grade 4 or
50. n Dexamethasone 4mg orally every 6 hours starting 24 hours pre chemo Dexamethasone 8mg IV 30 minutes pre chemo Chlorphenamine 10mg IV bolus dose 30 mins pre chemo Ranitidine 50mg IV bolus dose 30mins pre chemo Continue dexamethasone chlorphenamine and ranitidine for 24 48 hours after oxaliplatin Grade 3 and 4 Treat for full anaphylaxis DO NOT GIVE further oxaliplatin 29 Yttrium 90 SIR Spheres microspheres plus Ir MdG For additional Private Care only Summary This regimen is used where radioembolisation is added to the treatment of a patient already receiving IrMdG Prior to radioembolisatoin full dose IrMdG is used colorectal page 13 CTIS 751 For the radiembolisation cycle reduced dose IrMdG must be used see below CTIS 1745 Post radioembolisation reduced dose IrMdG may be still used for up to 2 cycles post radioembolisation Regimen must be confirmed by consultant Radio Embolisation Cycle Reduced dose IrMdG CTIS 1745 Atropine 250mcg SC bolus dose Day 1 lrinotecan 100mg m IV over 30 mins Day 1 Folinic acid 350mg IV over 2 hours Day 1 5Fluorouracil 400mg m IV bolus dose Day 1 5Fluorouracil 2400mg m IV over 46hours Day 1 Radio embolism using SIR spheres microspheres Day 3 yttrium 90 Consult manufacturers users manual for dose Dose calculated based on BSA tumour involvement and percentage lung shunting Post Radio Embolisation reduced dose IrMdG CTIS 1745 may be used for
51. n 5FU 3day 20 Streptozocin Modified Degramont 21 Streptozocin 5FU Cisplatin 22 Streptozocin Doxorubicin Anthracycline Regimens 23 Doxorubicin Systemic Dox 75 24 Epirubicin Systemic EPI 50 CHEMO EMBOLISATION 25 Cisplatin chemo embolisation 26 Doxorubicin chemo embolisation ADDITIONAL PRIVATE CARE REGIMENS Subject to local approval 27 EOX 28 Radio Embolisation SIR Spheres Modified OxMdG 29 Radio Embolisation SIR Spheres Modified IriMdG CHEMO RADIATION REGIMENS 30 5FU320 FA20 5days 31 Gemcitabine 300 RT 32 Capecitabine 1650 RT HpB Cancer Regimens Oct 2011 12 doc CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS CTIS 1228 1225 1222 1741 1739 1740 89 1742 1743 1744 1266 1704 1746 1745 204 1260 1028 HPB page 2 of 58 Page 33 33 34 35 35 37 38 39 39 40 41 42 51 55 56 NHS North West London Cancer Network HEPATO PANCREATICO BILIARY Including Neuroendocrine and GISTs Section by Dr Harpreet Wasan Dr Rohini Sharma and Dr Alexandra Taylor Version HPB Regimens v5 2 NWLCN 200ct1 1 Section last updated 19 September 2011 Section last corrected 20 October 2011 Approved by GI Oncology Lead Clinician September 2011 Approved by WLCN HPB Tumour Group September 2011 Review Date September 2012 Tumour Markers Diagnosis Tumour Markers Cholangiocarcinoma CA19 9 CEA CA125 Duodenal ca
52. ncer CA19 9 CEA Gall Bladder CA19 9 CEA Pancreas CA19 9 CEA CA125 Hepatocellular Alpha fetoprotein aFP Neuro endocrine SHIAA Fasting GI peptide screen CGa NSE alpha fetoprotein aFP If tumour markers not elevated at baseline not necessary to repeat with every cycle Chemotherapy Alone No radiotherapy 5 Fluorouracil Single Agent Regimens Folinic Acid Folinic acid refers to the mixed race mix D and L isomers Calcium levofolinate refers to L folinic acid isomer only 1 DeGramont Modified MdG via CVAD CTIS 734 via NS CTIS 1219 Folinic Acid 350mg IV over 2 hours Day 1 5 Fluorouracil 400mg m IV bolus Day 1 5 Fluorouracil 2800mg m IV over 46 hours Days 1 to 2 Interval between cycles Repeat every 14 days Number of cycles HPB 6 12 cycles 3 6 months Tests before starting course of chemo FBC U amp Es LFTs INR if hepatocellular cancer diagnosis Tumour markers in table on page 3 Tests to OK Confirm each cycle of chemo FBC U amp Es LFTs INR if hepatocellular cancer diagnosis Supportive drugs with each cycle Low risk antiemetics as per NWLCN guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Loperamide if required 2 4mg QDS prn Max 16mg 24hours Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions
53. ncreatic origin in adults with progressive disease HpB Cancer Regimens Oct 2011 12 doc HPB page 31 of 58 Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs Tests before starting course of chemo Tests to OK confirm each cycle of chemo Supportive drugs with each cycle Patient information FBC U amp Es LFTs fasting blood glucose chest X Ray serum cholesterol and triglycerides Tumour markers page 3 Treat existing infections before commencing treatment FBC U amp Es LFTs Fasting blood glucose every 4 weeks Serum cholesterol and triglycerides every 4 weeks Chest X Ray 4 weeks No routine supportive drugs Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book NWLCN Chemotherapy alert card Macmillan drug specific information sheets NWLCN Neutropenia DVD Additional information Swallow whole with a glass of water with our without food at the same time each day Do not crush or chew If a dose is missed do not take and additional dose but take the usual prescribed next dose Patient should be advised to report promptly any new worsening respiratory symptoms Avoid live vaccines during treatment Dose modifications Table Everolimus Dose Modification Side Effect Everolimus Haematology Neutrophils Platelets Hb x10 L x10 L g dL 21 0 and 250 and 29 lt 1 0 and or lt 50 and or
54. nd liver abscess from infection of necrotic tumour Haematological Discuss with consultant There is some evidence that there is a decrease in leukocyte lymphocyte and neutrophils levels following RE with a nadir 6 8 weeks after the RE procedure The mechanism of leucopenia is unknown although current clinical data 2009 suggest this adverse effect may have clinical sequelae when RE is used in combination with systemic radiosensitisers eg 5FU Oxaliplatin HpB Cancer Regimens Oct 2011 12 doc HPB page 48 of 58 Table OxMdG Side effect OxMdG Dose Modification Source Focus Trial SPC Coin Trial Haematology Coin Neutrophils Platelets x10 L x10 L gt 1 5 and gt 75 lt 1 5 or lt 75 If more than 1 delay or 1 delay gt 2 weeks Neutrophils lt 1 0x10 L_at any time SPC Myelotoxicity more frequent 30 with OxMdG than with MdG Full dose all drugs Delay 1 week then recheck FBC Only give if neutrophils and platelets above these limits Lower limit for platelets is due to possible mild thrombocytopenia after a number of cycles of OxMdG Wait for full recovery then Oxaliplatin Full dose 5FU Omit bolus dose but give full dose infusion Continue without bolus dose on subsequent cycles If further delays for myelotoxicity occur despite 20 dose reduction discuss with consultant Oxaliplatin 25 dose reduction in addition to any 5FU reduction above Renal Func
55. ne Delay until until recovery then until recovery then recovery then give restart with full dose epirubicin 25 oxaliplatin dose reduction 100mg m lt 0 5 or 25 49 Delay oxaliplatin Stop capecitabine Delay until until recovery then until recovery then recovery then give restart with full dose epirubicin 50 oxaliplatin dose reduction 100mg m Oxaliplatin Capecitabine Epirubicin Any and lt 25 Delay oxaliplatin Stop capecitabine Do not give until recovery then until recovery then restart with full dose oxaliplatin 100mg m HpB Cancer Regimens Oct 2011 12 doc HPB page 43 of 58 Side effects EOX Dose Modifications Source REAL 2 Neutropenic fever OR Grade 3 infection fever with neutropenia ANC lt 1 at any time Grade 4 infection fever with neutropenia ANC lt 1 at any time Reduce to Full dose on Epirubicin 25 oxaliplatin subsequent cycles dose reduction on 100mg m on subsequent cycles subsequent cycles Reduce to Full dose on Epirubicin 50 oxaliplatin subsequent cycles dose reduction on 100mg m on subsequent cycles subsequent cycles Hepatic function SPC Real 2 Bilirubin Either AST or ALT lt 1 5x ULN and 2 5 x ULN 1 5 3 0x ULN and 22 5 x ULN gt 3 0x ULN and gt 2 5 x ULN Full dose Full dose Full dose Discuss with Full dose Do not give consultant Discuss with Stop capecitabine Do not give consultant Discuss with consultant Renal function
56. nic acid 350mg IV over 2 hours Day 1 Oxaliplatin 60mg m IV over 2 hours Day 1 5Fluorouracil 400mg m IV bolus dose Day 1 5Fluorouracil 2400mg m IV over 46hours Day 1 Cycle 5 to 12 As cycle 1 Interval between cycles Repeat every 14 days as detailed above Number of cycles For additional private care only Only for loco regional treatment of HCC confined to liver Hepatocellular carcinoma with Childs Pugh A or possible good B 12 cycles ie one radioembolisation Tests before starting course of chemo e Preliminary arteriogram of liver within 32 days of RE to determine HpB Cancer Regimens Oct 2011 12 doc HPB page 46 of 58 vascular anatomy of the liver to provide road map of arterial supply of liver to plan delivery of SIR spheres see User manual e Break through macro aggregated albumin MAA nuclear scan within 32 days of RE to calculate percentage of SIR spheres that will pass through the liver and lodge in lungs due to arteriovenous shunts Dose must be adjusted to limit y damage to lung see SIR spheres User manual e Contrast enhanced helical CT scan to calculate tumour involvement needed to calculate SIR sphere dose see SIR sphere users manual FBC U amp Es LFTs Crcl calculated Do EDTA if s lt 60mls min INR tumour markers in table on page 3 Childs Pugh score Tests to OK confirm each cycle of chemo FBC U amp Es LFTs INR Childs Pugh score Supportive drugs with each cycle High risk antie
57. nitor BP and dipstick urine for protein before each cycle Can be treated with standard antihypertensives and discuss with consultant Temporary suspension is recommended in patients with severe hypertension not controlled with medical management Sunitinib treatment may be resumed once hypertension is appropriately controlled Renal function SPC No clinical studies have been performed in patients with impaired renal function Hepatic function SPC No dose adjustment is recommended when administering sunitinib to patients with mild moderate Child Pugh Class A or B hepatic impairment Sunitinib has not been studied in patients with Child Pugh Class C hepatic impairment HpB Cancer Regimens Oct 2011 12 doc HPB page 30 of 58 15 Sunitinib 37 5 Continuous CTIS 1736 Apply to London Cancer Drugs Fund for funding Sunitinib 37 5mg Oral Once a day Days 1 to 28 Interval between cycles Repeat every 28 days ie no rest period Number of cycles Apply to London Cancer Drugs fund for unresectable or metastatic pancreatic neuroendocrine tumours excluding poorly differentiated tumours with disease progression Continue until progressive disease In line with NICE TA179 for Unresectable and or metastatic malignant GIST if e Imatininb treatment has failed because of resistance or intolerance and e The drug cost of sunitinib excluding any related costs for the 1 cycle is met by the manufacturers Continu
58. nt Grade 3 Full dose all drugs Stop capecitabine start loperamide 2 4mg QDS prn oral max 16mg 24hrs or codeine phosphate 30 60mg oral QDS If diarrhoea resolves within 2 days restart all drugs full dose If diarrhoea persists wait until recovery then restart Capecitabine dose reduction as per SPC table page 20 As for Grade 2 but if grade 3 4 diarrhoea recurs despite appropriate capecitabine dose reduction then reduce oxaliplatin dose to 100mg m in subsequent cycles Hand Foot Syndrome SPC Grade 1 gt Grade 2 Stop capecitabine until recovery Once recovered restart full dose all drugs Stop capecitabine until recovery Once recovered restart chemo with dose according to SPC table page 20 Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended Neurotoxicity REAL 2 Cold related dysaethesia Lasting 1 7 days Lasting gt 7 days Persistent between cycles Full dose Full dose Oxaliplatin withhold until recovery then restart oxaliplatin at 100mg m If recurs despite dose reduction omit oxaliplatin in subsequent cycles Discuss carboplatin substitution with consultant Parasthesia without pain Lasting 1 7 days Lasting gt 7 days Persistent between cycles Full dose Full dose Oxaliplatin withhold until recovery then restart oxaliplatin at 100mg m If recurs despite dose reduction omit oxa
59. of 5FU induced hand foot syndrome Pyridoxine is not recommended DPD Deficiency Focus 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU catabolism Discuss with consultant Cardiotoxicity Focus Uncommon 5FU may provoke angina or MI in patients with ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment Neurotoxicity Focus Uncommon Cerebellar Consider alternative non 5FU treatment 2 Lokich 5FU 300 Contin CTIS 221 300mg m day 5 Fluorouracil IV continuous infusion for 12 weeks Continuous infusion for 12 weeks 1 cycle 3 weeks Repeat tests every 21 days Interval between cycles Number of cycles HPB Tests before starting course of chemo Tests to OK Confirm each cycle of chemo Supportive drugs with each cycle Patient information Continuous infusion for 12 to 24 weeks 4 to 8 cycles of 21 days 12 24 weeks FBC U amp Es LFTs Tumour markers in table on page 3 FBC U amp Es LFTs Low risk antiemetics as per NWLCN guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Loperamide 2mg QDS PRN max 16mg 24hours Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as a
60. on analgesia to map out HpB Cancer Regimens Oct 2011 12 doc HPB page 41 of 58 Tests before each cycle anatomy of hepatic arteries and confirm patency of portal vein FBC U amp Es LFTs INR tumour markers in table on page 3 Childs Pugh score cardiac assessment Check lifetime cumulative doxorubicin dose does not exceed 450mg mIlifetime FBC U amp Es LFTs INR Childs Pugh score Supportive drugs with each cycle Fluids only 3 hours before procedure Patient information Additional information Dose modification Reference Prophylactic antibiotics 1 hour pre procedure Lipiodol as above Embolisation particles PVA as above Prophylactic antibiotics post procedure Low risk antiemetics as per NWLCN guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Alopecia can occur with only 1 cycle See Doxorubicin Epirubicin table page 40 Additional Private Care Regimens 27 EOX CTIS 1704 Epirubicin 50mg m IV bolus Day 1 Oxaliplatin 130mg m IV over 2 hours Day 1 Capecitabine 625mg m Orally twice a day Days 1 to 21 ie total 1250mg m day with water after a meal See dose table page 17 Interval between cycles Repeat every 21 days Number of cycles Subject to local approval funding 6 cy
61. ood flow from the arterial vasculature rather than the portal venous system and this characteristic ensures that the microspheres become lodged in the malignant microvasculature Since RE delivers high doses of ionising radiation to the tumour compartment whilst maintaining radiation exposure of the normal liver to a tolerable level it can be regarded as a form of brachytherapy It has also been termed selective internal radiotherapy SIRT Yttrium 90 SIR Spheres microspheres plus OxMdG For Additional Private Care Summary Cycle 1 Full dose OxMdG CTIS 327 Cycle 2 Radio embolisation plus reduced dose OxMdG CTIS 1746 Cycle 3 Reduced dose OxMdG CTIS 1746 Cycle 4 Reduced dose OxMdG CTIS 1746 Cycle 5to12 Full dose OxMdG CTIS 327 Cycle 1 Full dose OxmdG CTIS 327 Folinic acid 350mg IV over 2 hours Day 1 Oxaliplatin 85mg m IV over 2 hours Day 1 5Fluorouracil 400mg m IV bolus dose Day 1 5Fluorouracil 2400mg m IV over 46hours Day 1 Cycle 2 only Radio embolism plus reduced dose OxMdG CTIS 1746 Folinic acid 350mg IV over 2 hours Day 1 Oxaliplatin 60mg m IV over 2 hours Day 1 5Fluorouracil 400mg m IV bolus dose Day 1 5Fluorouracil 2400mg m IV over 46hours Day 1 Radio embolism using SIR spheres microspheres Day 3 yttrium 90 Consult manufacturers users manual for dose Dose calculated based on BSA tumour involvement and percentage lung shunting Cycles 3 and 4 Reduced dose OxMdG CTIS 1746 Foli
62. ook Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Performing CT scans before 4 6 months of treatment is usually non informative Dose modifications Reference Table Imatinib Side effect Imatinib Dose Modification SPC Hepatic function SPC Mainly hepatic excretion Only 13 excretion through kidney SPC Bilirubin gt 3xULN Or Transaminases gt 5xULN Stop treatment until bilirubin lt 1 5xULN and transaminases lt 2 5xULN Treatment may be resumed at reduced dose If previous dose 400mg reduce to 300mg Haematology SPC Neutrophils Platelets x10 L x10 L lt 1 0 and or lt 50 15t occurrence 2 occurrence Stop treatment until neutrophils gt 1 5 and platelets gt 75 Resume treatment at original 400mg adult dose In event of recurrence of neutrophils lt 1 0 x 10 L and or platelets lt 50x10 L stop treatment until neutrophils gt 1 5 and platelets gt 75 then resume with reduced dose Eg if previous dose 400mg reduce to 300mg Imatinib is a cytochrome P450 substrate dose increases should be made eg 50 increase when used concurrently with potent enzyme inducers eg rifampicin phenytoin 13 Sorafenib CTIS 1735 Apply to London Cancer Drugs Fund for funding Sorafenib 400mg Oral twice a day Continuous treatment Consid
63. oxaliplatin from 85mg m to 65mg m metastatic setting or 75mg m adjuvant sec If parasthesia persist until next cycle omit oxaliplatin give HpB Cancer Regimens Oct 2011 12 doc HPB page 49 of 58 Side effect OxMdG Dose Modification Source Focus Trial SPC Coin Trial DeGramont alone until fully resolved Resumption of oxaliplatin may be considered once fully resolved Check dose with consultant src Stomatitis Coin If mouth ulcers occur despite chlorhexidine mouthcare delay until recovery to grade 1 or less then 5FU 20 dose reduction bolus and infusion If further toxicity occurs despite above reductions then SFU 40 dose reduction bolus and infusion Oxaliplatin 20 dose reduction Diarrhoea Coin Between cycles Not resolved by next cycle Unresolved If Grade 4 diarrhoea neutrophils lt 1 0 and platelets lt 50 spc Between cycles treat symptomatically loperamide 2 4mg QDS max 16mg 24hrs and or codeine phosphate 30 60mg QDS as required Not resolved by next cycle Delay 1 week until resolved If problematic despite symptomatic treatment or more than 1 delay give SFU 20 dose reduction bolus and infusion Oxaliplatin 20 dose reduction If further toxicity occurs despite above dose reduction then SFU Oxaliplatin 20 dose reduction bolus and infusion further 20 dose reduction Delay until recovered then reduce oxaliplatin from 85mg m
64. pearance Interrupt capecitabine until resolved to grade 0 to 1 Interrupt capecitabine until resolved to grade 0 to 1 Discontinue capecitabine treatment permanently Capecitabine 25 dose reduction Capecitabine 50 dose reduction Do not give Grade 4 1 appearance Discontinue permanently If consultant considers it is in best interest of patient to continue interrupt capecitabine until resolved to grade 0 to 1 Capecitabine 50 dose reduction 8 CX Cisplat 60 Cape1250_ CTIS 1707 Prehydrations Day 1 Cisplatin 6O0mg m IV over 2hrs Day 1 Post hydrations Day 1 Capecitabine 625mg m Oral twice a day after Days 1 to 21 Interval between cycles Number of cycles Tests before starting course of chemo Tests to OK Confirm each cycle of chemo Supportive drugs with each cycle Patient information ie total 1250mg m7 day HPB Repeat every 21 days 4 8 cycles FBC U amp Es Mg LFTs Crcl calculated meals with food Do EDTA if lt 60mls min tumour markers in table on page 3 Baseline ECG if history of ischaemic heart disease or cardiac risk factors FBC U amp Es Mg LFTs Crcl calculated Do EDTA if rising serum creatinine Very high risk antiemetics as per NWLCN guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sh
65. post procedure High risk antiemetics as per NWLCN guidelines or as per local policy Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information Dose modification Discuss with consultant Reference 26 Doxorubicin Chemoembolisation CTIS 1266 This is only indicated if approved by Liver MDT and no evidence of portal venous involvement Fluids only for 3 hours before procedure Day 1 Prophylactic antibiotics 1 hour before procedure Day 1 Selective cannulation of hepatic artery arteries supplying the tumour Day 1 Then Doxorubicin 60mg flat dose mixed by radiologists and given intra arterially Day 1 Lipiodol 4 10mls Followed by Embolisation with PVA particles gt 300microns Intra arterially Day 1 any component may be omitted if clinically indicated Antibiotics post procedure Interval between cycles 6 10 weeks if patient shows no persistent ill effects Number of cycles Only for loco regional treatment of HCC confined to liver Hepatocellular carcinoma with Child s Pugh A or possible good B Aim for 2 cycles if tolerated May be repeated beyond 2 cycles in selective good responses Tests before starting course of chemo Preliminary hepatic artery angiography under local anaesthetic sedati
66. ppropriate Neutropenia DVD NWLCN Additional Information Administration notes Dose modifications See page 4 Table Lokich page 6 References Lokich et al J Clin Oncol 1989 7 425 32 J Clin Oncol 2001 Webb et al ECF HpB Cancer Regimens Oct 2011 12 doc HPB page 5 of 58 Table Lokich NB Palliative patients will require greater dose reductions than stated below based on individual patient parameters Discuss with consultant Side effect Lokich Dose Modification Source CRO06 Trial Haematology WBC lt 2 0x10 L OR Platelets lt 75x 10 L Interrupt infusion for 1 week or until recovery Resume with 5FU reduce dose by 50mg m day Renal function GFR below 30ml min Unclear guidance Discuss with consultant Hepatic function Unclear guidance Discuss with consultant Stomatitis CR06 Routine mouthcare with chlorhexidine If still a problem stop chemo until recovery then Restart with 5FU Reduce by 50mg m7 day Diarrhoea CR06 Give loperamide 2 4mg QDS or codeine phosphate 30 60mg QDS If still a problem stop chemo until recovery then Restart with 5FU Reduce by 50mg m7 day Hand Foot Syndrome 2Grade 2 Stop chemo until recovered then restart with 5FU dose reduced by 50mg m day Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of 5FU induced hand foot syndrome Pyridoxine is not recommended DP
67. progression HPB page 28 of 58 Tests before starting course of chemo Tests to OK confirm each cycle of chemo Supportive drugs with each cycle Patient information Additional information FBC U amp Es LFTs BP dipstick protein 24 hour urine protein quantitative analysis tumour markers in table on page 3 FBC U amp Es LFTs BP dipstick urine 24 hour urine protein quantitative analysis every 4 5 weeks thyroid function tests every 8 weeks Chlorhexidine mouthwash 10mls QDS Loperamide 2mg QDS PRN Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Administration notes SPC Sunitinib may be taken with our without food If a dose is missed the patient should not be given an additional dose The patient should take the usual prescribed dose on the following day Dose modifications Table Sunitinib Sunitinib dose reductions may be made in 12 5mg decrements depending on the type and severity of toxicity as outlined below Side effect Sunitinib Dose Modification Sunitinib vs Sorafenib trial in advanced HCC Non Haematological Toxicities eg diarrhoea hand foot fatigue mucositis Grade 1 Grade 2 Grade 3 1 appearance Recurrent Grade 4 Continue at the same dose level Continue at
68. reptozocin painful if given too quickly See table below Side effect Strep 5FU Cisp Dose Modification HpB Cancer Regimens Oct 2011 12 doc HPB page 37 of 58 Haematology Neutrophils Platelets x10 L x10 L gt 1 5 and gt 100 Full dose lt 1 5 or lt 100 Do not give Discuss with consultant Diarrhoea gt Grade 2 5FU 25 dose reduction Renal function DI Oncol Handbook 2004 Cisplatin standardised in Mar09 based on ABC02 Crcl 260mls min Full dose 50 59mls min Cisplatin 25 dose reduction 5FU and streptozocin full dose 40 49mls min Cisplatin 50 dose reduction Streptozocin 25 dose reduction 5FU Full dose lt 40mls min Do not give cisplatin Discuss with consultant Proteinuria Streptozocin Consider dose reduction or stopping streptozocin 22 Strep Dox CTIS 89 Doxorubicin Streptozocin Interval between cycles Number of cycles 50mg m IV bolus Day 1 and 22 500mg m IV over 4 hours Days 1 to 5 Repeat every 6 weeks Neuroendocrine tumours resistant disease 4 cycles and reassess Tests before starting course of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis tumour markers indicated in table on page 3 Test to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis every other cycle every 6 weeks Dipstick for proteinuria with every c
69. rnative with consultant significant high frequency loss on audiogram 6 MdG CISP60 Modified De Gramont Cisplatin 60 CTIS Prehydrations Day 1 Cisplatin 60mg m IV over 1 hour Day 1 Folinic acid 350mg IV over 2 hours Day 1 5 Fluorouracil 400mg m IV bolus Day 1 5 Fluorouracil 2400mg m IV over 46 hours Days 1 2 Interval between cycles Repeat every 14 days Number of cycles HPB 6 12 cycles 3 6 months Tests before starting course of chemo FBC U amp Es Mg LFTs Crcl calculated Do EDTA if lt 60mls min INR if hepatocellular cancer diagnosis Tumour markers indicated in table on page 3 Tests to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl calculated Do EDTA if rising serum creatinine INR if hepatocellular cancer diagnosis Supportive drugs with each cycle Very high risk antiemetics as per NWLCN Patient information Additional information guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Loperamide if required 2 4mg QDS prn Max 16mg 24hours Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Administration notes See ECF page 10 Dose modifications References DeGramont e Annals Oncol HpB Cancer Regimens Oct 2011 12 doc See DeGramont modified table page
70. route so exposure might be increased in patients with severe hepatic impairment Discuss with consultant HpB Cancer Regimens Oct 2011 12 doc HPB page 27 of 58 Side effect Sorafenib Dose Modification Nexavar SPC A6181170 trial Dermatological toxicities SPC Hand foot skin reactions Palmar Plantar erythrodysaesthesia and rash represent most common adverse drug reactions to Sorafenib Rash and hand foot skin reactions are usually CTC Grade 1 and 2 and generally appear during the first 6 weeks of treatment Discuss with consultant Management may include topical therapies for symptomatic relief temporary treatment interruption and or dose modification and in severe or persistent cases permanent discontinuation of Sorafenib Arterial Hypertension SPC Monitor BP and dipstick urine for protein before each cycle Can be treated with standard antihypertensives and discuss with consultant spc Hypertension is usually mild to moderate occurs early in the course of treatment and is amenable to management with standard antihypertensive therapy In cases of severe or persistent hypertension or hypertensive crisis despite institution of antihypertensive therapy permanent discontinuation of sorafenib should be considered Haemorrhage SPC An increased incidence of bleeding may occur following sorafenib administration If any bleeding necessitates medical intervention it is recommended that permanent discon
71. ry infusion pump via a central venous access device CVAD refer to relevant protocol for care of CVAD Joint care with the community nursing services should be arranged in advance to support the patient and to assist with disconnecting the chemotherapy and flushing the CVAD Written community nursing referrals should be completed and the patient should be discharged with a home spillage kit sharps container and a small supply of equipment to flush the line and dress the entry site of the CVAD Capecitabine Patients must receive specific capecitabine counselling prior to treatment from a capecitabine trained nurse pharmacist as per local policy Patients must be given written and verbal information on capecitabine including how to take the tablets when to stop ie In the event of toxicity and after 14 days and whom to contact when side effects occur Written information should be sent to the patient s GP Capecitabine tablets should be taken with water 30 minutes after food and approximately 12 hours apart Capecitabine interacts with warfarin and phenytoin and therefore patients on these drugs must have their blood levels monitored more regularly Capecitabine is contraindicated with allopurinol Dose modifications Table ECX page 19 Reference ASCO Abstract REAL 2 HpB Cancer Regimens Oct 2011 12 doc HPB page 18 of 58 Table ECX NB Palliative patients will require greater dose reductions than above based on individual patient parameters Di
72. s and information prescriptions as appropriate Neutropenia DVD NWLCN If borderline proteinuria patient may need to do dipstick urine analysis at home Additional information Streptozocin painful if given too quickly Dose modifications See table Strep 5FU on page 34 Reference Strep 5FU 3 day CTIS 1741 Streptozocin 500mg m IV over 4 hours Days 1 to 3 5 Fluorouracil 400mg m IV over 1hour Days 1 to 3 Interval between cycles Repeat every 3 4 weeks Number of cycles Neuroendocrine tumours 4 cycles and reassess Tests before starting course of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis tumour markers as indicated in table on page 3 Test to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis with every 5 week cycle Dipstick for proteinuria with every cycle Supportive drugs with each cycle High risk antiemetics as per NWLCN guidelines or as per local policy Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN If borderline proteinuria patient may need to do dipstick urine analysis at home Additional information Streptozocin painful if given too quickly Dose modifications See table Strep 5FU on page 34 Refer
73. scuss with consultant Side effects ECX Haematology REAL 2 Neutrophils Platelets x 10 L x 10 L gt 1 0 and 275 0 5 0 9 or 50 74 lt 0 5 or 25 49 Any and lt 25 Neutropenic fever OR Grade 3 infection fever with neutropenia ANC lt 1 at any time Grade 4 infection fever with neutropenia ANC lt 1 at any time Dose Modifications Source REAL 2 Cisplatin Full dose Delay until recovered then full dose Delay until recovery then full dose Delay until recovery then full dose Full dose on subsequent cycles Full dose on subsequent cycles Capecitabine Full dose Stop capecitabine until recovery then full dose Stop capecitabine until recovery then full dose Stop capecitabine until recovery then full dose Full dose on subsequent cycles Full dose on subsequent cycles Epirubicin Full dose Delay until recovery then give epirubicin 25 dose reduction Delay until recovery then give epirubicin 50 dose reduction Do not give Epirubicin 25 dose reduction on subsequent cycles Epirubicin 50 dose reduction on subsequent cycles Renal function GFR REAL2 SPC Cisplatin standardised Mar 09 based on ABC02 gt 60mls min 50 59 mls min 40 49mls min 30 39mls min lt 30mls min Full dose Cisplatin 25 dose reduction Cisplatin 50 dose reduction Do not give Do not give Full dose Full dose Capecitabine SPC recommends no dose adjust
74. seline then reduce the dose by 1 dose level ie reduce dose by 12 5mg and resume treatment Lymphopenia Grade 3 or Grade 4 Patients who develop grade 3 or 4 lymphopenia may continue treatment without interruption Drug Interactions SPC CYP3A4 Inducers eg rifampicin Co administration of potent CYP3A4 inducers may DECREASE sunitinib plasma concentrations Combination with inducers should therefore be avoided If this is not possible the dose of sunitinib may need to be increased See SPC CYP3A4 Inhibitors eg ketoconazole Co administration of potent CYP3A4 inhibitors may INCREASE sunitinib plasma concentrations Selection of an alternative concomitant medication with no minimal or minimal enzyme inhibition potential is recommended If this is not possible the dosage of sunitinib may been to be reduced See SPC Skin discolouration SPC Yellow skin discolouration occurs in approximately 30 of patients Depigmentation of hair or skin may also occur Also dryness thickness or cracking of skin blister or rash on palms soles These events not cumulative were typically reversible and generally did not result in treatment discontinuation Haemorrhage SPC An increased incidence of bleeding may occur following sunitinib administration These events may occur suddenly If any bleeding necessitated medical intervention then permanent discontinuation of sunitinib should be considered Hypertension SPC Mo
75. sheets and information prescriptions as appropriate Neutropenia DVD NWLCN See Gem 1g Cisp60 page 22 Table Gem 1g Cisp 60 below Table Gem 1g Cisp 60 Side effect Gem1g Cisp60 Dose Modification A8C02 trial Haematology Neutrophils Platelets x10 L x10 L gt 1 0 and gt 100 0 5 0 9 or 50 99 lt 0 5 or lt 50 Full dose all drugs Delay until recovery Discuss with consultant if gt 3 weeks Then Cisplatin Full dose Gemcitabine 25 dose reduction Day 1 8 Delay until recovery Discuss with consultant if gt 3 weeks Then Cisplatin 25 dose reduction Gemcitabine 25 dose reduction Renal function NLCN Cisplatin Standardised Mar09 based on ABC02 CrCl gt 60mls min 50 59mls min 40 49mls min lt 40mls min If sudden increase in creatinine investigate to rule out haemolytic uraemic syndrome NB Under 60mls min do EDTA or omit cisplatin Full dose all drugs Cisplatin 25 dose reduction Gemcitabine full dose Cisplatin 50 dose reduction Gemcitabine full dose Do not give regimen Biliary tract obstruction No liver metastases Bilirubin gt 1 5 x ULN Stop chemo until resolved below these levels ALT AST ALP gt 3 0 x ULN With liver metastases Bilirubin gt 1 5 x ULN Stop chemo until resolved below these levels ALT AST ALP gt 5 0 x ULN Lethargy Grade 3 4 Consider gemcitabine 25 dose reduction If does not respond to dose reduction stop treatment HpB
76. should have pre treatment evaluation of cardiac function with MUGA scan or equivalent If left HPB page 17 of 58 ventricular ejection fraction is less than 50 prior to treatment then omit epirubicin Tests to OK Confirm each cycle of chemo FBC U amp Es Mg LFTs Crcl calculated Do EDTA if rising serum creatinine Supportive drugs with each cycle Very high risk antiemetics as per NWLCN guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS Loperamide 2 4mg QDS orally PRN Max 16mg day Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Patient must attend nurse capecitabine counselling clinic for cycle 1 and 2 of ECX Take capecitabine after meals and with water Additional information Administration notes Cisplatin Weigh patient before and after cisplatin infusion or monitor urine output If weight gain gt 1 5kg or symptomatic of fluid retention inform doctor patient may require diuretics Inpatients should be on a fluid balance chart and weighed daily Average urine output of at least 100ml hr is expected during and for 6 hours after cisplatin infusion Outpatients should be encouraged to drink 3 litres of fluid within the following 24 hours 5 Fluorouracil If 5FU administered using an ambulato
77. sipating within 24 hours but it may require narcotic analgesia in about one third of patients It is routinely managed by prophylactic pre medication Lethargy Post RE treatment lethargy approximately 40 of cases may occur anywhere between 1 week and 8 weeks post treatment and can last up to 10 days Nausea Post RE treatment mild nausea 40 50 of cases is most common in patients who have received multiple courses of chemo Symptoms rarely last more than 24 hours and can be managed by prophylactic antiemetics medication Gastritis Duodenitis Ulceration Discuss with consultant One of the most common potentially serious complications Incidence rate of gastritis duodenitis can be reduced by experience and meticulous attention to the administration procedure so as to ensure that there is minimal chance of SIR spheres entering small arteries supplying the gut Radiation Hepatitis Discuss with consultant The other most common potentially serious complication Radiation hepatitis is largely but not totally preventable by using correct SIR sphere dose and making allowances for dose reduction where there is increased risk of causing radiation damage such as in poor liver reserve or small volume tumour mass in liver see SIR Sphere user manual Pancreatitis Discuss with consultant Rare complication is acute pancreatitis resulting from SIR sphere refluxing back down hepatic artery and lodging in the pancreas a
78. teinuria Streptozocin consider dose reduction or stopping streptozocin HpB Cancer Regimens Oct 2011 12 doc HPB page 36 of 58 21 Streptozocin 5FU Cisplatin CTIS 1740 Streptozocin 5Fluorouracil Cisplatin Post hydrations Interval between cycles Number of cycles 1000mg m IV over 4 hours Day 1 500mg m IV over 1 hour Day 1 60mg m IV over 2 hours Day 1 Repeat every 21 days Neuroendocrine tumours where frequent weekly appointments problematic 4 cycles then reassess Can be repeated Tests before starting course of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis tumour markers as indicated in table on page 3 Test to OK Confirm each cycle of chemo FBC U amp Es LFTs Crcl with 24 hour urine protein quantitative analysis with every other cycle Dipstick for proteinuria with every cycle Review treatment if proteinuria Supportive drugs with each cycle High risk antiemetics as per NWLCN Patient information Additional information Dose modifications Reference Table Strep 5FU Cisp guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN If borderline proteinuria patient may need to do dipstick urine analysis at home St
79. the same dose level Withhold dose until toxicity is lt grade 1 or has returned to baseline Then resume treatment at the same dose level Grade 3 hypophosphatemia without clinical symptoms Discuss with consultant If toxicity recurs with grade 3 severity withhold dose until toxicity is lt grade 1 or returned to baseline Discuss with consultant and reduce the dose by 1 dose level ie reduce dose by 12 5mg and resume treatment Withhold dose until toxicity is lt grade 1 or has returned to baseline Discuss with consultant and either reduce the dose by 1 dose level ie reduce dose by 12 5mg or discontinue Grade 4 hyperuricaemia without clinical symptoms discuss with consultant Haematological side effects other than lymphopenia Grade 1 Grade 2 Grade 3 1 appearance Continue at same dose level Continue at same dose level Withhold dose until toxicity is lt grade 2 or has returned to HpB Cancer Regimens Oct 2011 12 doc HPB page 29 of 58 Side effect Sunitinib Dose Modification Sunitinib vs Sorafenib trial in advanced HCC Recurrence Grade 4 baseline then resume treatment at the same dose level If the toxicity recurs with grade 3 severity withhold dose until toxicity is lt grade 2 or baseline Discuss with consultant and reduce the dose by 1 dose level ie reduce dose by 12 5mg and resume treatment Withhold dose until toxicity is lt grade 2 or has returned to ba
80. tinuation of sorafenib should be considered Do not administer sorafenib within 28 days before or after surgery Cardiac events SPC Increased incidence of treatment emergent cardiac ischaemic infarction events with sorafenib compared to placebo Temporary or permanent discontinuation of sorafenib should be considered in patients who develop cardiac ischaemia and or infarction NB Patients with unstable coronary artery disease or recent MI were excluded from sorafenib studies GI Perforation SPC GI perforation is an uncommon event reported in less than 1 of patients taking sorafenib In some cases this was not associated with apparent intra abdominal tumour If GI perforation discontinue sorafenib Drug Interactions SPC Sorafenib is metabolised primarily in the liver see SPC for detailed section on drug interactions 14 Sunitinib 50 with break CTIS 1737 Apply to London Cancer Drugs Fund for funding Sunitinib Interval between cycles Number of cycles HpB Cancer Regimens Oct 2011 12 doc 50mg Oral Once a day Days 1 to 28 Repeat every 42 days ie 4 weeks treatment followed by 2 week rest period In line with NICE TA179 for Unresectable and or metastatic malignant GIST if e Imatininb treatment has failed because of resistance or intolerance and e The drug cost of sunitinib excluding any related costs for the 1 cycle is met by the manufacturers Continue until disease
81. tion Coin Crel gt 30mls min lt 30mls min Oxaliplatin Not nephrotoxic but is renally cleared If Crcl calculated is lt 60mls min do EDTA Full dose all drugs Oxaliplatin Omit 5 FU 25 dose reduction bolus and infusion Hepatic Function Coin AST ALT gt 5 x ULN Bilirubin gt 3 x ULN gt 51micromol l NB Significantly impaired hepatic function may be a sign of disease progression ie review treatment Oxaliplatin not principally cleared by liver but is evidence of delayed clearance in patients with marked hepatic dysfunction Withhold 5FU until recovery Oxaliplatin 50 dose reduction 5 Fluorouracil 50 dose reduction bolus and infusion Neurotoxicity Paraesthesia of hands and feet Dysaesthesia in throat often precipitated by cold Oxaliplatin peripheral sensory symptoms 5FU uncommon and cerebellar Consider other chemo regimen These symptoms are precipitated by cold If symptoms lasts few hours to a few days after oxaliplatin administration no treatment or dose reduction required Acute laryngopharyngeal dysaesthesia during or within the hours following the oxaliplatin 2 hour infusion administer next oxaliplatin over 6 hours spc If symptoms last longer than 7 days and are troublesome reduce oxaliplatin dose from 85mg m to 65mg m metastatic setting or 75mg m adjuvant src If parasthesia without functional impairment persists until the next cycle reduce
82. to 65mg m metastatic or to 75mg m adjuvant plus 5FU 20 dose reduction bolus and infusion Hand Foot Syndrome 2Grade 2 5FU 20 dose reduction bolus and infusion Phase III randomised controlled trials show no benefit from pyridoxine for prevention or treatment of SFU induced hand foot syndrome Pyridoxine is not recommended DPD Deficiency Focus 1 3 of patients have markedly exaggerated 5FU toxicity due to reduced 5FU Catabolism Discuss with consultant Cardiotoxicity Focus Uncommon 5FU may provoke angina attack or MI in ischaemic heart disease Seek specialist opinion on upgraded anti anginal medication and consider dose reduction or alternative non 5FU treatment HpB Cancer Regimens Oct 2011 12 doc HPB page 50 of 58 Side effect OxMdG Dose Modification Source Focus Trial SPC Coin Trial Allergic reactions to oxaliplatin Approximately 9 1 SPC incidence of acute hypersensitivity to oxaliplatin usually after more than 6 cycles have been administered During administration patient may develop rash fever swollen mouth tongue hyper or hypotension etc This rarely develops to full blown anaphylaxis even with repeated treatment Grade 1 and 2 If acute hypersensitivity occurs e Discontinue infusion e Treat with IV corticosteroids and antihistamine e After full recovery continue with SFU FA alone e Rechallenge at consultant s discretion with coi
83. tten information should be sent to the patient s GP Capecitabine interacts with warfarin and phenytoin and therefore patients on these drugs must have their blood levels monitored more regularly Capecitabine is contraindicated with allopurinol Epirubicin Vesicant follow WLCN administration policy Oxaliplatin Oxaliplatin is incompatible with normal saline therefore the venous access device and administration sets should be flushed with 5 glucose Patients should be advised to keep warm as exposure to cold post oxaliplatin infusion may aggravate symptoms of peripheral neuropathy and laryngopharyngeal dysthesia In the event of laryngopharyngeal symptoms during an oxaliplatin infusion reassure the patient that the symptoms are likely to resolve This must not be confused with an allergic response which requires emergency intervention The patient who suffers from laryngopharyngeal spasm may be re challenged with oxaliplatin at a slower infusion rate of up to 6 hours On occasions pain may be experienced in the infusion arm if so slow infusion rate to a maximum 6 hours Consider CVAD if problematic Dose modifications Table EOX below Reference ASCO Abstract REAL 2 Table EOX Side effects EOX Dose Modifications Source REAL 2 Haematology REAL 2 Oxaliplatin Capecitabine Epirubicin Neutrophils Platelets x 10 L x 10 L gt 1 0 and gt 75 Full dose Full dose Full dose 0 5 0 9 or 50 74 Delay oxaliplatin Stop capecitabi
84. uidelines or as per local policy Patient information Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN Additional information See Gem 1g Cisp60 HPB page 22 Dose modifications See Gemcitabine D1 8 15 table page 23 Reference J Clin Oncol 1997 6 2403 13 Burris et al HpB Cancer Regimens Oct 2011 12 doc HPB page 24 of 58 Table Gemcitabine D1 8 15 Side effect Gem D1 8 15 Dose Modification ABC 02 Haematology Neutrophils Platelets x 10 L x 10 L gt 1 0 and gt 100 0 5 0 9 or 50 99 lt 0 5 or lt 50 Full dose all drugs Delay until recovery Discuss with consultant if gt 3 weeks Otherwise Gemcitabine 25 dose reduction Days 1 8 and15 Delay until recovery Discuss with consultant if gt 3 weeks Otherwise Gemcitabine 25 dose reduction Days 1 8 and 15 Renal function NLCN 2009 gt 30mls min lt 30mls min If sudden increase in creatinine investigate to rule out haemolytic uraemic syndrome Gemcitabine full dose Do not give regimen Biliary tract obstruction No liver metastases Bilirubin gt 1 5 x ULN ALT AST ALP gt 3 0 x ULN With liver metastases Bilirubin gt 1 5 x ULN ALT AST ALP gt 5 0 x ULN Stop chemo until resolved below these levels Stop chemo until resolved b
85. ycle Review treatment if proteinuria Supportive drugs with each cycle High risk antiemetics as per NWLCN Patient information Additional information Dose modifications Reference Table Strep Dox guidelines or as per local policy Chemotherapy treatment booklet local information Macmillan Your chemotherapy record NWLCN red book Chemotherapy alert card NWLCN Macmillan drug specific information sheets and information prescriptions as appropriate Neutropenia DVD NWLCN If borderline proteinuria patient may need to do dipstick test for urine analysis at home Streptozocin painful if given too quickly See table below Side effect Strep Dox Dose Modification HpB Cancer Regimens Oct 2011 12 doc HPB page 38 of 58 Side effect Strep Dox Dose Modification Haematology Do not give Discuss with consultant Neutrophils Platelets x10 L x10 L 2A and gt 100 lt 1 5 or lt 100 Proteinuria Full dose Consider dose reduction or stopping stretozocin Streptozocin Renal impairment DI Oncol Handbook 2004 gt 50ml min 10 49mls min lt 10ml min Full dose Streptozocin 25 dose reduction Discuss with consultant Consider streptozocin 50 dose reduction Hepatic function Bilirubin lt 19micromol L 20 51micromol L 52 84micromol L gt 85micromol L If AST 2 3xULN Full dose Doxorubicin Epirubicin 50 dose reduction Doxorubicin Epirubi

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