COLORECTAL REGIMENS Section by: Dr Pippa …

1 COLORECTAL REGIMENS . Section by: Dr Pippa Riddle, Dr Riz Ahmad, Dr Suzy Cleator, Dr Harpreet Wasan, Dr Charles Lowdell. Version: COLORECTAL REGIMENS APPROVED NWLCN 11th July 2014. Section last updated: 11th July 2014 Section last corrected 11th July 2014. Approved by GI Oncology Lead Clinician: Dr P Riddle Date Review date: July 2016. INDEX Page COLORECTAL CANCER: Chemotherapy alone (No radiotherapy). 5 Fluorouracil Single Agent +/- Folinic Acid 1. MAYO 5FU 425/FA 20 5 day 3. 5FU 370/FA 20 5 day 3. 2. Degramont 5. 3. Lokich/5FU-300 contin 7. Oral Fluoropyrimidine Single Agent 4. Capecitabine 2500. 14 day (DeGramont substitute) 9. Tegafur with uracil (Uftoral) Discontinued by manufacturer March 2013 removed Irinotecan 5.

2 IrMdG Irinotecan-Degramont (FOLFIRI) 11. 6. Capiri Irinotecan-Capecitabine 1600 (CAPIRI) 14. 7. Irinotecan Single Agent 17. Oxaliplatin 8. OxMdG Oxaliplatin-Degramont (FOLFOX) 19. 9. Capox Oxaliplatin-Capecitabine 2000 23. Ox-Ralt Oxaliplatin-Raltitrexed (see page 34). Mitomycin 10. 26. 11. MitoC-Capecitabine 2500 27. 12. MitoC-MdG 30. Raltitrexed (Tomudex). 13. Raltitrexed Single Agent 32. 14. Raltitrexed-Oxaliplatin (TOMOX) 34. COLORECTAL REGIMENS APPROVED NWLCN 11 Jul14 no tracked REGIMENS APPROVED NWLCN COLORECTAL Page 1 of 79. Page Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibodies General advice on prophylaxis against EGFR skin reactions 35. Cetuximab (Erbitux). Funding of cetuximab 35.

3 15. Cetuximab-OxMdG Cetux-Oxaliplatin-MdG NICE/ Cancer Drugs Fund 37. 16. Cetuximab-reduced Capox Cetux-Oxali-Capecitabine 1700 NICE/Cancer Drugs Fund 40. 17. Cetuximab-IrMdG Cetux-Irinotecan-MdG NICE/Cancer Drugs Fund 42. 18. Cetuximab-Capiri Cetux-Irino-capecitabine 1600 NICE/Cancer Drugs Fund 44. 19. Cetuximab Single Agent weekly Cancer Drugs Fund 46. 20. Cetuximab Single Agent every 2 weeks Cancer Drugs Fund 47. Panitumumab (Vectibix). 21. Panitumumab-OxMdG Cancer Drugs Fund 47. Vascular Endothelial Growth Receptor (VEGF) Inhibitors Aflibercept 22. Aflibercept-IrMdG Aflibercept-Irinotecan-MdG Cancer Drugs Fund 49. Bevacizumab (Avastin). Funding of Bevacizumab 54. 23. Bevacizumab-OxMdG Bev-Oxaliplatin-MdG Cancer Drugs Fund 54.

4 24. Bevacizumab-Capox Bev-Oxaliplatin-Capecitabine 2000 Cancer Drugs Fund 59. 25. Bevacizumab-IrMdG Bev-Irinotecan-MdG Cancer Drugs Fund 60. 26. Bevacizumab-Capiri Bev-Irinotecan-Capecitabine 1600 Cancer Drugs Fund 61. 27. Bevacizumab-Cape Bev-Capecitabine 2500 Cancer Drugs Fund 62. Embolisation (Additional Private Care). 28. SIR-spheres embolisation - OxMdG reduced dose Additional Private Care 63. COLORECTAL CANCER: Chemo radiation REGIMENS Chemo-Radiation Dose Modifications 66. 29. Bossett Regimen 5FU 350/FA 20 + RT 67. 30. Capecitabine1650 + RT 68. ANAL CANCER. ANAL CANCER Chemo-radiation REGIMENS 31. Mitomycin/5FU + RT, UKCCR Regimen local disease 70. ANAL CANCER Chemotherapy Alone 32. Cisplatin-5FU.

5 CISP-60-5FU 4 day 72. 33. Docetaxel 100 Single Agent (Additional Private Care) 73. WHO Performance status 75. Cockcroft Gault formula 75. Version Control Box 76. COLORECTAL REGIMENS APPROVED NWLCN 11 Jul14 no tracked REGIMENS APPROVED NWLCN COLORECTAL Page 2 of 79. COLORECTAL REGIMENS . Section by: Dr Pippa Riddle, Dr Riz Ahmad, Dr Suzy Cleator, Dr Harpreet Wasan, Dr Charles Lowdell. Version: COLORECTAL REGIMENS APPROVED NWLCN 11 Jul14. Section last updated: 11thJuly 2014 Last corrected: 11th July 2014. Approved by GI Oncology Lead Clinician: July 2014. Review date: July 2016. CHEMOTHERAPY ALONE (No radiotherapy). 5-Fluorouracil Single Agent REGIMENS +/- Folinic Acid Folinic acid refers to the mixed racemix D and L isomers.

6 Calcium levofolinate refers to L folinic acid isomers only. MAYO Adaptations: 1. 5FU425/FA20 5day or 5FU 370/FA20 5day Folinic Acid 20mg/m2 IV bolus Days 1 to 5. 5 Fluorouracil dose determined by age see below Dose under 70 years 425mg/m2 IV bolus Days 1 to 5. and ECOG 1. Dose over 70 years 370mg/m2 IV bolus Days 1 to 5. and/or ECOG 2. Interval between cycles: Repeat every 28 days Number of cycles: Colon cancer Neoadjuvant up to 6 cycles/6 months Adjuvant up to 6 cycles/6 months Metastatic/local recurrence 3-6 cycles/3-6 months Tests before starting course of chemo: FBC, U&Es, LFTs, tumour markers CEA, CA19-9. Tests to OK/Confirm each cycle of chemo: FBC, U&Es, LFTs Supportive drugs with each cycle: Low risk antiemetics as per NWLCN.

7 Guidelines or as per local policy Chlorhexidine mouthwash 10mls QDS. Loperamide 2-4mg QDS PRN. Patient information: Chemotherapy treatment booklet (local information/Macmillan). Your chemotherapy record (Red book). Chemotherapy alert card Macmillan drug specific information sheet(s) 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 4-5. References: J. Clin Oncol 1997 15:246-50. O'Connell et al Ann. Oncol 1998 9 (5):535-41. Borner MM. COLORECTAL REGIMENS APPROVED NWLCN 11 Jul14 no tracked REGIMENS APPROVED NWLCN COLORECTAL Page 3 of 79.

8 J. Clin Oncol 1989 7(10):1407-18 (425mg). J. Clin Oncol 1991;9:449-52 (ice chips). Table: MAYO (Ref. QUASAR protocol UKCCCR 1998). Radical treatment only: For combination of Haematological/non Haematological toxicity Wait until FULL recovery ie. neutrophils x109/L and platelets 100 x109/L and/or any persistent mucositis and diarrhoea have resolved. If resolved within 2 weeks restart chemo using dose modifications below. 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 x109/L x109/L 0-1 2 3 4. And 100 Full dose Full dose Delay until Do not give recovery to toxicity grade 2 then give 50% dose reduction * And/or 50-99 Delay until Delay until Delay until full Do not give haematological haematological haematological Discuss with consultant as in recovery then recovery then and non- some cases may go ahead with neutrophils to provided give full dose give 20% dose haematological platelets 100 reduction recovery to toxicity grade 2 then give 50% dose reduction 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 grade

9 2 then give 50% dose reduction < Or <25 Delay until Delay until Delay until full Do not give haematological haematological haematological recovery then recovery then and non- give 50% dose give 50% dose haematological reduction reduction recovery to toxicity grade 2 then give 50% dose reduction Do not dose reduce Folinic Acid COLORECTAL REGIMENS APPROVED NWLCN 11 Jul14 no tracked REGIMENS APPROVED NWLCN COLORECTAL Page 4 of 79. Side-Effect: MAYO Dose Modification (Source:Quasar/FOCUS trials). Haematology See above Renal function GFR 30mls/min Unclear guidance. Discuss with consultant Hepatic function Unclear guidance. Discuss with consultant Stomatitis Routine mouthcare with chlorhexidine. Ensure ice chips are being used during administration of 5FU.

10 If still a problem reduce dose according to table above Diarrhoea Give loperamide 2-4mg oral QDS PRN (max 16mg/day). or codeine phosphate 30-60mg oral QDS PRN. If still a problem reduce dose according to table above Hand-Foot Syndrome Reduce dose according to table page 4. Phase III randomised controlled trials show no benefit for 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.