CCC Chemotherapy Protocols V9.0

CCC Chemotherapy Protocols V9.0 General observations 3 Breast cancer 5 Gastrointestinal cancer Oesophagus 17 Gastric 19 Pancreas 22 Cholangiocarcinoma 24 Hepatocellular carcinoma 25 Neuroendocrine tumours 26 Colorectal 28 Anal 37 Gynaecological cancer Ovarian 38 Endometrial 44 Cervix 46 Haematological Hodgkins disease 50 Non-Hodgkins Lymphoma 51 Head and Neck cancer 55 Thyroid 58 Lung cancer Small cell 59 Non-small cell 62 Mesothelioma 67 Melanoma 68 Sarcomas Soft tissue sarcomas 69 Osteosarcoma 71 Ewings sarcoma 73 Fibromatosis 78 Rhabdomyosarcoma 79 GIST 81 Urological cancer Bladder 82 Renal 85 Prostate 87 Germ Cell 89 Primary CNS malignancy 93 Unknown Primary 98 Issue Date: 30 th April 2012 Page 1 of 120 Filename: MCHACPROTO Issue No: 9.0

(continued) Page Emergency chemotherapy drugs 98 Bone metastases 99 Antiemetic protocols 101 GCSF policy 104 Prophylactic antibiotics 104 Erythopoietin policy 105 Intra-thecal chemotherapy policy 105 Wright formula 106 Cisplatin / carboplatin doses 106 Cisplatin hydration policy 107 Haematological parameters 108 Capecitabine renal function recommendations 108 Neutropenic sepsis policy 109 Platelet transfusion policy 110 Hypocalcaemia 110 Hypomagnesaemia 110 Ifosfamide renal toxicity and encephalopathy 111 Folinic acid rescue for high dose methotrexate 111 CCC dose banding policy 112 Surface Area Nomogram 119 North West Cancer Drugs Fund 120 Issue Date: 30 th April 2012 Page 2 of 120 Filename: MCHACPROTO Issue No: 9.0

General observations There is now an electronic version of the protocol book which is available on CCO Comms. This will be updated monthly and represents the working version of the book. It also contains more information and will have a hyperlink to the nurse work instructions for each protocol. The paper version will continue but will only be updated annually. Protocol Additions 2011-12 Maintenance pemetrexed in advanced NSCLC Pazopanib in advanced renal cell carcinoma Gefitinib in advanced NSCLC In addition we have included all drugs currently funded by the Cancer Drugs Fund. Cancer Drugs Fund A number of treatments are now available via the Cancer Drugs Fund. The process for accessing the fund is as follows: Complete the relevant application form which can be found on the North West Cancer Drugs Fund web site. The easiest way to find this is to type nw cancer drugs fund into google and select the application forms button in the header on the home page. E-mail the completed form to the pharmacy dept at CCC using: ccftr.cytopharmacy@nhs.net this address can be found by typing cco pharmacy into the address book in outlook. The form will be checked in pharmacy and sent to the network pharmacist who will coordinate approval by the cdf. All request which fulfil the criteria are approved automatically and the process usually takes about a week. Off Protocol Treatment Policy Inevitably situations will arise that are not covered by the standard CCC protocols. Consultants who wish to use a non-protocol regimen should complete the non-protocol treatment form and submit it to the Clinical Director for Chemotherapy for approval at least 5 days prior to the date of cycle 1 of the proposed treatment. All reasonable requests will be granted. Trials Entry to clinical trials should be considered for all patients but individual studies have not been listed due to frequent changes. Issue Date: 30 th April 2012 Page 3 of 120 Filename: MCHACPROTO Issue No: 9.0

Co-payments / top-ups / additional private care The uptake of co-payments has been minimal and will be further reduced by by the introduction of the Cancer drugs fund. However the process is still in place and is outlined below. Co-payment refers to top-up funding by an NHS patient for an otherwise unavailable treatment. NHS policy allows patients to fund elements of their care not currently available on the NHS without losing their entitlement to continue with free NHS care. The CCC co-payments policy considers access to systemic cancer treatments - chemotherapy or targeted therapies - that are currently not funded for use in NHS patients. A copy of the policy can be obtained from pharmacy or found on the CCC website and includes all the required documentation: Co-payment algorithm Additional Private Treatment Form Patient information leaflet. Financial agreement forms. The self-funded drug may be a single agent or given in combination with standard treatments, in which case the costs incurred relate only to the self-funded drug. However it should always be clear which components of treatment are privately funded and which are provided as NHS treatments. The patient commits to self-funding the treatment for the duration of the entire programme under supervision by the responsible consultant i.e. a specific number of cycles or indefinite period while there is evidence of a maintained benefit and response. This will include the costs of treatment preparation and delivery, payment of any investigations needed, and any supportive care drugs given as a direct consequence of receiving the self-funded treatment. Issue Date: 30 th April 2012 Page 4 of 120 Filename: MCHACPROTO Issue No: 9.0

Breast Cancer Adjuvant Epi-CMF Epirubicin 100mg/m 2 iv day 1 repeated at 21 day intervals x 4 cycles followed by CMF x 4 cycles if LV ejection fraction prior to cycle 1 if history of cardiac problems. Standard fbc limits for administration apply CMF Cyclophosphamide 100mg/m 2 po days 1-14 in divided doses Methotrexate 40mg/m 2 iv days 1 and 8 5-Fluorouracil 600mg/m 2 iv days 1 and 8 For patients unable to tolerate oral cyclophosphamide substitute iv cyclophosphamide 600mg/m 2 days 1 and 8 Folinic acid rescue not normally required unless patients develop signs of Methotrexate toxicity, then 15mg 6 hourly x 6 doses starting 24hrs post Methotrexate with subsequent cycles Cycles are repeated at 28 days from day 1 to a total of 6 cycles. if but Methotrexate is hazardous in the presence of renal insufficiency, not required on day 8 Standard fbc limits for administration apply AC Doxorubicin 60mg/m 2 + cyclophosphamide 600mg/m 2 iv day 1 repeated at 21 day intervals for 4 cycles has been shown to be equivalent to 6 cycles of CMF. if LV ejection fraction prior to cycle 1 if history of cardiac problems Standard fbc limits for administration apply Issue Date: 30 th April 2012 Page 5 of 120 Filename: MCHACPROTO Issue No: 9.0

EC Epirubicin 90mg/m 2 IV + cyclophosphamide 600mg/m 2 IV day 1 repeated at 21 day intervals for 4 cycles. Alternative to AC in this situation FEC / Docetaxel if LV ejection fraction prior to cycle 1 if history of cardiac problems Standard fbc limits for administration apply This protocol is available for node +ve patients according to NICE guidance Patients may receive primary prophylaxis with pegfilgrastim after each cycle FEC 5-Fluorouracil 500mg/m 2 IV day 1 Epirubicin 100mg/m 2 IV day 1 Cyclophosphamide 500mg/m 2 IV day 1 Repeat at 21 day intervals for 3 cycles if LV ejection fraction prior to cycle 1 if history of cardiac problems Standard fbc limits for administration apply Followed by Docetaxel 100 mg/m 2 iv x 3 cycles at 21 day intervals Pre-medication: Dexamethasone 8mg oral bd x 3 days start 24hrs pre-docetaxel if Standard fbc limits for administration apply NB: See section on advanced disease for dose modifications and precautions. Issue Date: 30 th April 2012 Page 6 of 120 Filename: MCHACPROTO Issue No: 9.0

Trastuzumab For patients who fit HERA trial inclusion criteria Non-metastatic potentially operable primary invasive breast cancer HER2 positive (IHC 3+ and / or FISH positive) Completed definitive surgery and radiotherapy Completed at least 4 cycles of adjuvant or neoadjuvant chemotherapy Within 9 weeks of chemotherapy / radiotherapy / surgery, whichever is last. ECOG PS 0 or 1 Baseline LVEF > 55% after completing chemotherapy No serious cardiac illness Trastuzumab 8mg/kg iv loading dose over 90min then 6mg/kg over 60min and thereafter over 30 min every 3 weeks for 12 months (18 cycles) if no problems. Stop at any time if CCF develops LVEF at 3, 6, 9 and 12 months Stop trastuzumab if LVEF falls by 10 points or to <50% Repeat after 3-4 weeks and if LVEF: 50+ continue with trastuzumab 44-49 and within 10 points of baseline continue with trastuzumab < 44 stop trastuzumab Neo-adjuvant Indication / Treatment plan Patients with locally advanced disease or to allow less radical surgery in patients with operable tumours. Options include six cycles of EC/AC or four cycles EC/AC followed by four cycles docetaxel at 100mg/m 2 HER-2 +ve patients may commence trastuzumab following completion of anthracycline based treatment ie concurrently with docetaxel if this is being given provided LVEF normal after completion of the anthracycline. Patients should then have the remaining 14 cycles of trastuzumab as adjuvant treatment. Issue Date: 30 th April 2012 Page 7 of 120 Filename: MCHACPROTO Issue No: 9.0

AC/EC Doxorubicin 60mg/m 2 iv day 1 or Epirubicin 90mg/m 2 iv day 1 + Cyclophosphamide 600mg/m 2 iv day 1 Repeat at 21 day intervals for up to 6 cycles. Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if LV ejection fraction prior to cycle 1 if history of cardiac problems Standard fbc limits for administration apply Docetaxel 100 mg/m 2 iv q 21 days x 4 cycles Pre-medication: Dexamethasone 8mg oral bd x 3 days start 24hrs pre-docetaxel if Standard fbc limits for administration apply NB: See section on advanced disease for dose modifications and precautions. Issue Date: 30 th April 2012 Page 8 of 120 Filename: MCHACPROTO Issue No: 9.0

Advanced disease First line Doxorubicin 75mg/m 2 iv day 1 Repeat at 21 day intervals usually to a maximum of 6 cycles AC Doxorubicin 50mg/m 2 iv day 1 Cyclophosphamide 500mg/m 2 iv day 1 Repeat at 21 day intervals usually to a maximum of 6 cycles if LV ejection fraction prior to cycle 1 if history of cardiac problems Docetaxel 75-100 mg/m 2 iv day 1 q 21 days, max 6 cycles Pre-medication: Dexamethasone 8mg oral bd x 3 days start 24hrs pre-docetaxel Criteria Previously received full dose anthracycline as adjuvant therapy or Less than six months since anthracycline based adjuvant therapy or Unsuitable for anthracycline therapy NB: See section on 2 nd /3 rd line treatment for dose modifications and precautions. if Issue Date: 30 th April 2012 Page 9 of 120 Filename: MCHACPROTO Issue No: 9.0

Docetaxel / Capecitabine Docetaxel 75mg/m 2 iv day 1 + Capecitabine 1000mg/m 2 bd oral days 1-14 NB see capecitabine renal function recommendations p105 Pre-medication Dexamethasone 8mg bd x 3 days start 24hrs pre-docetaxel Repeat at 21 day intervals, max 6 cycles Criteria PS 0-1 NB very fit patients only Recurrent following adjuvant anthracycline therapy if Paclitaxel / Gemcitabine Paclitaxel 175mg/m 2 iv day 1 Gemcitabine 1250mg/m 2 iv days 1 and 8 Pre-medication Chlorpheniramine 10mg Dexamethasone 16mg Ranitidine 50mg Repeat at 21 day intervals, max 6 cycles Criteria PS 0-1 NB very fit patients only Recurrent following adjuvant anthracycline therapy if Issue Date: 30 th April 2012 Page 10 of 120 Filename: MCHACPROTO Issue No: 9.0

CMF Cyclophosphamide 100mg/m 2 po days 1-14 in divided doses Methotrexate 40mg/m 2 iv days 1 and 8 5-Fluorouracil 600mg/m 2 iv days 1 and 8 Folinic acid rescue not normally required unless patients develop signs of Methotrexate toxicity, then 15mg 6 hourly x 6 doses starting 24hrs post Methotrexate with subsequent cycles For patients unable to tolerate oral cyclophosphamide substitute iv cyclophosphamide 600mg/m 2 days 1 and 8 if but care if renal function significantly deranged, not required day 8 Standard fbc limits for administration apply Cycles are repeated at 28 days from day 1 to a total of 6 CMF (iv) Cyclophosphamide 600mg/m 2 iv day 1 Methotrexate 40mg/m 2 iv day 1 5-Fluorouracil 600mg/m 2 iv day 1 Folinic acid rescue not normally required unless patients develop signs of Methotrexate toxicity, then 15mg 6 hourly x 6 doses starting 24hrs post Methotrexate with subsequent cycles Cycles repeated every 21 days to a maximum of 6 if but consider omitting Methotrexate if renal function abnormal *Bevacizumab 10mg/kg iv infusion Repeat at 14 day intervals Criteria Advanced disease Triple negative First line chemotherapy In combination with paclitaxel *NB available via the Cancer Drugs fund *Eribulin cycle 1.4mg/m 2 eribulin mesylate (equivalent to 1.23mg/m 2 eribulin) iv days 1 and 8 of a 21 day Criteria At least 2 prior chemotherapy regimens for advanced disease Evidence of response to prior chemotherapy *NB available via the Cancer Drugs fund Issue Date: 30 th April 2012 Page 11 of 120 Filename: MCHACPROTO Issue No: 9.0

Patients with compromised liver or marrow function Doxorubicin 20mg/m 2 iv weekly for patients with compromised liver or marrow function due to tumour infiltration Ensure normal renal function prior to cycle 1 and repeat during subsequent cycles if clinically indicated Patients with abnormal hepatic function should be treated cautiously LV ejection fraction prior to cycle 1 if history of cardiac problems. Normal limits for administration apply with the exception that for patients with marrow infiltration treatment may be continued at lower platelet and neutrophil counts at treating physician discretion. Continue with weekly treatment usually for 6-8 weeks before changing to fortnightly or 21 day cycles depending on response. Maximum total dose 450mg/m 2 Paclitaxel 80mg/m 2 iv weekly for patients with compromised liver or marrow function who have previously received anthracyclines. Pre-medication Dexamethasone Chlorpheniramine Ranitidine 8mg iv before first cycle 4mg iv before second and subsequent cycles 10mg iv 50mg iv Laboratory investigations Ensure normal renal function prior to cycle 1 and repeat during subsequent cycles if clinically indicated Patients with abnormal hepatic function should be treated cautiously. Normal limits for administration apply with the exception that for patients with marrow infiltration treatment may be continued at lower platelet and neutrophil counts at treating physician discretion. Issue Date: 30 th April 2012 Page 12 of 120 Filename: MCHACPROTO Issue No: 9.0

Second or Third line Vinorelbine 25-30mg/m 2 iv day 1 and 8 of a 21 day cycle. or 60-80mg/m 2 oral day 1 and 8 of a 21 day cycle Repeat at 21 days from day 1 Reassess after every 2 cycles, maximum 6 cycles Criteria: WHO performance status 0-1 Endocrine resistant Prior alkylating agent therapy if Docetaxel 75-100mg/m 2 iv q21 days maximum 6 cycles or 60-75mg/m 2 if moderately impaired liver function / heavily pre-treated / extensive bone metastases NB: severe toxicity may result in patients with major impairment of liver function Reassessment after two cycles and continue to a maximum of 6 only if responding or stable disease. Pre-medication Dexamethasone 8mg bd x 3 days commence 24 hours pretreatment if Issue Date: 30 th April 2012 Page 13 of 120 Filename: MCHACPROTO Issue No: 9.0

Capecitabine 1000-1250mg/m 2 oral twice daily for 14 days followed by 7 days off or 850-1000mg/m 2 twice daily for 14 days followed by 7 days off if heavily pre-treated or elderly NB see capecitabine renal function recommendations p105 Repeat at 21 days from day 1 for up to six cycles. Criteria Failed or unsuitable for anthracycline and/or taxane PS 0-2 if Bisphosphonate Zoledronic acid 4mg iv in 100mls Sodium chloride 0.9% over 15-30 minutes repeated at 28 day intervals. Criteria: Performance status 0-2 Symptomatic / extensive bone metastases Calcium supplements: Patients should have their serum calcium measured every four weeks and Adcal D3 tablets prescribed as necessary. Renal impairment Cr clearance Dose >60 4.0mg 50-60 3.5mg 40-49 3.3mg 30 39 3.0mg < 30 no treatment Serum creatinine should be repeated every 4 weeks and if it rises significantly during treatment zoledronic acid should be witheld until the creatinine has returned to within 10% of the baseline prior to starting. For patients with creatinine clearance < 30ml/min ibandronic acid 50mg weekly oral may be considered. *This is available via the off-protocol mechanism Issue Date: 30 th April 2012 Page 14 of 120 Filename: MCHACPROTO Issue No: 9.0

Management of patients with HER2 +ve cancers Trastuzumab 4 mg/kg loading dose i.v. over 90 minutes followed by 2mg/kg/week i.v. over 30 minutes for 8 doses then 6mg/kg every 3 weeks over 30minutes. or 8mg/kg iv loading dose over 90min then 6mg/kg over 60min for one dose and then over 30 min thereafter if no problems every 3 weeks Criteria: Strongly HER2 positive (HER2 3+ by IHC or FISH positive) Trastuzumab given together with a taxane or vinorelbine as first or second line treatment or second / third line as a single agent. NB not with anthracycline and with care within close proximity to anthracycline therapy (< 6 months). LVEF: baseline ECHO/MUGA + 3 monthly repeat advised for patients receiving treatment with trastuzumab. Lapatinib (Tyverb ) + capecitabine Lapatinib 1250mg po daily continuously + Capecitabine 1000mg/m 2 oral twice daily for 14 days followed by 7 days off or 850mg/m 2 twice daily for 14 days followed by 7 days off if heavily pre-treated or elderly NB see capecitabine renal function recommendations p105 Repeat at 21 days until progression or toxicity. For some responding patients continuing with lapatinib alone may be the right approach if capecitabine toxicity becomes unacceptable. Criteria Prior anthracycline, taxane and trastuzumab PS 0-2 IHC 3+ or FISH +ve cancer if *Available via the Cancer Drug Fund Issue Date: 30 th April 2012 Page 15 of 120 Filename: MCHACPROTO Issue No: 9.0

*Paclitaxel Albumin (Abraxane ) 260mg/m 2 iv repeat at 21 day intervals Consider if no longer safe to continue with paclitaxel or docetaxel. Patients may be able to receive Abraxane with premedication and appropriate precautions. Criteria Metastatic breast cancer Situations where taxanes are indicated if *Available via the Cancer Drugs Fund Issue Date: 30 th April 2012 Page 16 of 120 Filename: MCHACPROTO Issue No: 9.0

Gastrointestinal Cancer Oesophageal Carcinoma Adjuvant Not currently recommended as standard therapy Neoadjuvant Cisplatin/5FU Cisplatin 80mg/m 2 iv day 1 5-Fluorouracil 1g/m 2 over 24hrs iv days 1-4 or Capecitabine 1000mg/m 2 bd x 14 days Locally advanced Repeat at 21 days for two cycles. Criteria PS 0-1 Cr Cl > 50ml/min Operable oesophageal cancer Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Chemo-radiation protocol Cisplatin/5FU Cisplatin 80mg/m 2 iv day 1 and 29 5Fluorouracil 1g/m 2 iv over 24hrs days 1-4 and 29-32 or Capecitabine 825mg/m 2 oral bd Mon-Fri during XRT + XRT followed by two additional cycles after completion of XRT Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Issue Date: 30 th April 2012 Page 17 of 120 Filename: MCHACPROTO Issue No: 9.0

Cisplat/Capecitabine + XRT (SCOPE trial protocol) Cisplatin 60mg/m 2 iv day 1 and 29 + Capecitabine 625mg/m 2 oral bd days 1-21 NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals for 4 cycles with radiotherapy concurrent with cycles 3 and 4 Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Metastastic Cisplatin/5FU Cisplatin 80mg/m 2 iv day 1 5-Fluorouracil 1g/m 2 iv over 24hrs days 1-4 or Capecitabine 1000mg/m 2 bd x 14 days Repeat at 21 day intervals, max 4-6 cycles Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Issue Date: 30 th April 2012 Page 18 of 120 Filename: MCHACPROTO Issue No: 9.0

Gastric / Adenocarcinomas of Gastro-oesophageal junction Carcinoma Neoadjuvant / Adjuvant For patients with operable cancers after initial staging ECF/X x 3 cycles Surgery -- ECF/X x 3 cycles ECF/X Epirubicin 50mg/m 2 iv day 1 Cisplatin 60mg/m 2 iv day 1 5-Fluorouracil 200mg/m 2 / day via continuous iv infusion for 21 days or Capecitabine 625mg/m 2 bd days 1-21 NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Locally advanced / metastatic ECF/X Epirubicin 50mg/m 2 iv day 1 Cisplatin 60mg/m 2 iv day 1 5-Fluorouracil 200mg/m 2 / day via continuous iv infusion for 21 days or Capecitabine 625mg/m 2 bd days 1-21 NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals for a maximum of 4-6 cycles Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Issue Date: 30 th April 2012 Page 19 of 120 Filename: MCHACPROTO Issue No: 9.0

EOF/X Epirubicin 50mg/m 2 iv day 1 Oxaliplatin 130mg/m 2 iv day 1 5-Fluorouracil 200mg/m 2 / day via continuous iv infusion for 21 days or Capecitabine 625mg/m2 bd days 1-21 NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals for a maximum of 4-6 cycles Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Cisplatin/fluoropyrimidine/Herceptin Cisplatin 80mg/m 2 iv day 1 5-Fluorouracil 1g/m 2 over 24hrs iv days 1-4 or Capecitabine 1000mg/m 2 bd x 14 days Repeat at 21 day intervals for 6 cycles Herceptin 8mg/kg iv day 1 loading dose 6mg/kg iv every 21 days until progression Criteria PS 0-1 Cr Cl > 50ml/min HER 2 status IHC 3+ or FISH +ve Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Issue Date: 30 th April 2012 Page 20 of 120 Filename: MCHACPROTO Issue No: 9.0

Second line Irinotecan 250mg/m 2 iv day one of a 21 day cycle repeat x 4 cycles Option to increase to 350mg/m 2 if well tolerated atropine 600ug s/c prior to irinotecan if Issue Date: 30 th April 2012 Page 21 of 120 Filename: MCHACPROTO Issue No: 9.0

Pancreatic cancer Adjuvant 5-Fluorouracil+Folinic acid 5-Fluorouracil 425mg/m 2 iv daily days 1-5 Folinic acid 50mg iv daily days 1-5 Cycles are repeated at 28 days for 6 cycles. NB: For patients over 70yrs and those with borderline performance status the dose of 5- Fluorouracil should be reduced to 370mg/m 2 per day. if Advanced First line Gemcitabine 1g/m 2 iv weekly for 3 weeks followed by one week break Repeat 28 day cycles for up to 6 cycles.. Criteria PS 0-2 R0, R1 resection M0 Gemcitabine + Capecitabine if NB: transaminases may rise during gemcitabine therapy Gemcitabine 1g/m 2 iv days 1, 8, 15 Capecitabine 825mg/m 2 po bd for 21 days NB see capecitabine renal function recommendations p105 Repeat 28 day intervals for up to 6 cycles. Criteria PS 0-1 if NB: transaminases may rise during gemcitabine therapy CA19-9 every 4 weeks Day 8 or 15 Platelets 75 99 x10 9 /l continue at full dose Platelets < 75x10 9 /l omit gemcitabine Issue Date: 30 th April 2012 Page 22 of 120 Filename: MCHACPROTO Issue No: 9.0

Gemcitabine 1g/m 2 iv weekly for 3 weeks followed by one week break Repeat 28 day cycles for up to 6 cycles. or iv weekly for seven weeks followed by one week break for first cycle then 3 weeks on, one off as above. Criteria PS 0-2 if NB: transaminases may rise during gemcitabine therapy CA19-9 every 4 weeks Day 8 or 15 Platelets 75 99 x10 9 /l continue at full dose Platelets < 75x10 9 /l omit gemcitabine Second line Ox-Cap Oxaliplatin 85 mg/m 2 iv day 1 Capecitabine 900mg/m 2 oral bd x 9 days NB see capecitabine renal function recommendations p105 Repeat at 14 day intervals for 6 cycles then reassessment Criteria PS 0-2 Relapse < 6 months post adjuvant chemotherapy Progression free interval > 3 months following first line therapy if Fbc and creatinine prior to each cycle with the exception that the lower limit for platelets for administration of Ox-Cap is 75 x 10 9 /l Issue Date: 30 th April 2012 Page 23 of 120 Filename: MCHACPROTO Issue No: 9.0

Cholangiocarcinoma / Gall Bladder Carcinoma Advanced Gemcitabine + Cisplatin Gemcitabine 1000mg/m 2 day 1 and 8 Cisplatin 25mg/m 2 day 1 and 8 Repeat at 21 day intervals for a maximum of 6 cycles Criteria PS 0-1 if CA19-9 every 4 weeks Gemcitabine 1g/m 2 iv weekly for 3 weeks followed by one week break Repeat 28 day cycles for 4-6 cycles. Criteria PS 0-2 if CA19-9 every 4 weeks Issue Date: 30 th April 2012 Page 24 of 120 Filename: MCHACPROTO Issue No: 9.0

ECF/EOX Epirubicin 50mg/m 2 iv day 1 Cisplatin 60mg/m 2 iv day 1 5-Fluorouracil 200mg/m 2 / day via continuous iv infusion or Oxaliplatin 130mg/m 2 iv day 1 Epirubicin 50mg/m 2 iv day 1 Capecitabine 625mg/m 2 bd days 1-21 NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals for a maximum of 4-6 cycles Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Hepatocellular carcinoma* Sorafenib Sorafenib Initial dose 200mg bd increasing to 400mg bd over 4 weeks to 400mg bd oral continuously Continue until disease progression Criteria PS 0-2 Normal bilirubin Transaminases < 2xULN Normal renal function Laboratory investigations Fbc, U/Es, LFTs prior to each cycle Where renal / hepatic function are abnormal treatment is at physician discretion Discontinue if deteriorating renal or liver function Normal fbc limits for administration apply *NB Available via the Cancer Drug Fund Issue Date: 30 th April 2012 Page 25 of 120 Filename: MCHACPROTO Issue No: 9.0

Neuroendocrine tumours High mitotic rate, anaplastic histology, clinically aggressive Etoposide / cisplatin Etoposide 120mg/m 2 iv days 1-3 Cisplatin 70mg/m 2 iv days 1 Laboratory investigations Repeat at 21 day intervals max 6 cycles Criteria PS 0-1 Cr cl > 50ml/min Patients with rapidly progressive disease Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Low mitotic rate, well differentiated histology, clinically indolent Somatostatin short acting analogue titrated to achieve maximum benefit then switch to long acting preparation *Everolimus (Afinitor ) 10mg oral daily Ensure normal renal and hepatic function prior to each cycle 1 Criteria First or Second line therapy *NB Only available via the Cancer Drug Fund Issue Date: 30 th April 2012 Page 26 of 120 Filename: MCHACPROTO Issue No: 9.0

*Sunitinib (Sutent ) 37.5mg oral daily Ensure normal renal and hepatic function prior to each cycle 1 Criteria No prior anti-vegf therapy *NB Only available via the Cancer Drug Fund Progression on first line therapy Streptozotocin/Doxorubicin Streptozotocin 500mg/m 2 iv days 1-5 repeat every 6 weeks Doxorubicin 50mg/m 2 iv day 1 repeat every 3 weeks if Issue Date: 30 th April 2012 Page 27 of 120 Filename: MCHACPROTO Issue No: 9.0

Colorectal Adjuvant 5FU/FA 5-Fluorouracil 370mg/m 2 iv + folinic acid 50 mg iv weekly x 24 weeks if Fbc prior to every fourth week Capecitabine 1250mg/m 2 oral twice daily for 14 days followed by 7 days off Consider 1000mg/m 2 for patients over 70yrs NB see capecitabine renal function recommendations p105 Repeat at 21 days from day 1 for eight cycles. if Repeat creatinine if OxMdG Consider for younger high risk patients Oxaliplatin 85 mg/m 2 iv day 1 Folinic acid 350mg flat dose two hour infusion day 1 5-Fluorouracil 400mg/m 2 15 minute bolus day 1 5-Fluorouracil 2400mg/m 2 46hr infusion day 1 Repeat at 14 day intervals for 12 cycles Not suitable for patients with pre-existing neuropathy or conditions predisposing to neuropathy if with the exception that the lower limit for platelets for administration of OxMdG is 75 x 10 9 /l OX-Cap may be used as an alternative (see below) Issue Date: 30 th April 2012 Page 28 of 120 Filename: MCHACPROTO Issue No: 9.0

Rectal cancer - Chemoradiation 5FU + XRT 5-Fluorouracil 1000mg/m 2 iv days 1-4 and 22-26 (or final week) Or 5-Fluorouracil 300mg/m 2 + Folinic acid 50mg iv weekly during the radiotherapy Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if Capecitabine + XRT Capecitabine 825mg/m 2 oral bd Mon-Fri during XRT NB see capecitabine renal function recommendations p105 Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if Fbc each week during chemotherapy 5FU/FA 5-Fluorouracil 300mg/m 2 iv + folinic acid 50 mg iv weekly during XRT if Fbc prior to every fourth week Issue Date: 30 th April 2012 Page 29 of 120 Filename: MCHACPROTO Issue No: 9.0

Advanced Colorectal Cancer First line Single agent MdG MdG: Folinic acid 350mg flat dose two hour iv infusion day 1 5-Fluorouracil 400mg/m 2 15 minute iv bolus day 1 5FU 2800mg/m 2 46hr iv infusion start day 1 repeat at 14 day intervals, re-evaluate after 6 cycles. if Capecitabine 1250mg/m 2 oral twice daily for 14 days Consider 1000mg/m 2 if age >70yrs NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals for a maximum of 6 cycles Ensure normal renal and hepatic function prior to cycle 1 if Fbc and creatinine prior to each cycle Issue Date: 30 th April 2012 Page 30 of 120 Filename: MCHACPROTO Issue No: 9.0

Combination chemotherapy Consider for good PS status patients with relatively bulky disease who need a more rapid response. IrinMdG Irinotecan 180mg/m 2 iv + atropine 600ug s/c prior to irinotecan MdG: Folinic acid 350mg flat dose two hour iv infusion day 1 5-Fluorouracil 400mg/m 2 15 minute iv bolus day 1 5-Fluorouracil 2400mg/m 2 46hr infusion start day 1 Repeat at 14 day intervals Review after 12 weeks and consider continuing to 24 weeks if: SD / response. Acceptable toxicity Criteria: PS 0-2 if I-Cap Irinotecan 180mg/m 2 iv + atropine 600ug s/c prior to irinotecan Capecitabine 900mg/m 2 oral bd x 9 days NB see capecitabine renal function recommendations p105 Repeat at 14 day intervals Review after 12 weeks and consider continuing to 24 weeks if: SD / response. Acceptable toxicity Criteria: PS 0-1 if Fbc and creatinine prior to each cycle Issue Date: 30 th April 2012 Page 31 of 120 Filename: MCHACPROTO Issue No: 9.0

OxMdG Oxaliplatin 85 mg/m 2 iv day 1 Folinic acid 350mg flat dose two hour iv infusion day 1 5-Fluorouracil 400mg/m 2 15 minute iv bolus day 1 5-Fluorouracil 2400mg/m 2 46hr iv infusion start day 1 Repeat at 14 day intervals for 6 cycles then reassessment Avoid in patients with pre-existing neuropathy if with the exception that the lower limit for platelets for administration of OxMdG is 75 x 10 9 /l Ox-Cap Oxaliplatin 85 mg/m 2 iv day 1 Capecitabine 900mg/m 2 oral bd x 9 days NB see capecitabine renal function recommendations p105 Repeat at 14 day intervals for 6 cycles then reassessment Avoid in patients with pre-existing neuropathy if Fbc and creatinine prior to each cycle with the exception that the lower limit for platelets for administration of Ox-Cap is 75 x 10 9 /l XELOX Oxaliplatin 130 mg/m 2 iv day 1 Capecitabine 1000mg/m 2 oral bd x 14 days NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals for 4 cycles then reassessment Avoid in patients with pre-existing neuropathy if. Issue Date: 30 th April 2012 Page 32 of 120 Filename: MCHACPROTO Issue No: 9.0

OxMdG + Cetuximab Oxaliplatin 85 mg/m 2 iv day 1 Folinic acid 350mg flat dose two hour iv infusion day 1 5-Fluorouracil 400mg/m 2 15 minute iv bolus day 1 5-Fluorouracil 2400mg/m 2 46hr iv infusion start day 1 Cetuximab Week 1 400mg/m 2 iv day 1 over 2 hours using 0.2um in-line filter Then 500mg/m 2 iv over 1 hour every 2 weeks Premedication Dexamethasone 8mg Chlorpheniramine 10mg Ranitidine 150mg Repeat at 14 day intervals for 6 cycles then reassessment if Fbc and biochemistry prior to each cycle with the exception that the lower limit for platelets for administration of OxMdG is 75 x 10 9 /l Criteria KRAS wild type cancer PS 0-1 Metastatic disease confined to the liver and potentially resectable if downsized Primary resected or resectable Avoid in patients with pre-existing neuropathy IrinMdG + Cetuximab Irinotecan 180mg/m 2 iv + atropine 600ug s/c prior to irinotecan Folinic acid 350mg flat dose two hour iv infusion day 1 5-Fluorouracil 400mg/m 2 15 minute iv bolus day 1 5-Fluorouracil 2400mg/m 2 46hr infusion start day 1 Cetuximab Week 1 400mg/m 2 iv day 1 over 2 hours using 0.2um in-line filter Then 500mg/m 2 iv over 1 hour every 2 weeks Premedication Dexamethasone 8mg Chlorpheniramine 10mg Ranitidine 150mg Repeat at 14 day intervals Review after 12 weeks and consider continuing to 24 weeks if: SD / response. Acceptable toxicity if Fbc and biochemistry prior to each cycle with the exception that the lower limit for platelets for administration of OxMdG is 75 x 10 9 /l Criteria KRAS wild type cancer PS 0-1 Metastatic disease confined to the liver and potentially resectable if downsized Primary resected or resectable Issue Date: 30 th April 2012 Page 33 of 120 Filename: MCHACPROTO Issue No: 9.0

*Bevacizumab 14 day schedules: Bevacizumab 5mg/kg iv infusion 21 day schedules Bevacizumab 7.5mg/kg iv infusion Criteria *NB Advanced colorectal cancer First line chemotherapy With oxaliplatin or Irinotecan based combination chemotherapy Available via the Cancer Drug Fund Second / third line chemotherapy Irinotecan + MdG (see above) Oxaliplatin + MdG (see above) I-Cap (see above) Ox-Cap (see above) Irinotecan 180mg/m 2 iv day 1 of a 14 day cycle atropine 600ug s/c prior to irinotecan or 350mg/m 2 iv day one of a 21 day cycle atropine 600ug s/c prior to irinotecan Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if Where renal / hepatic function are abnormal treatment is at physician discretion Fbc prior to each cycle Normal fbc limits for administration apply Issue Date: 30 th April 2012 Page 34 of 120 Filename: MCHACPROTO Issue No: 9.0

*Irinotecan + Cetuximab Criteria - Must have KRAS wild type cancers - Previously responded to chemotherapy - Second or third line chemotherapy - performance status (0-1) Cetuximab Week 1 400mg/m 2 iv day 1 over 2 hours using 0.2um in-line filter Then 500mg/m 2 iv over 1 hour every 2 weeks Irinotecan 180mg/m 2 iv every 2 weeks + atropine 600ug s/c Premedication Dexamethasone 8mg Chlorpheniramine 10mg Ranitidine 150mg Continue until progression / unacceptable toxicity *Available via the Cancer Drug Fund * Cetuximab single agent Criteria - Must have KRAS wild type cancers - Previously responded to chemotherapy - third line chemotherapy - performance status (0,1) Cetuximab Week 1 400mg/m 2 iv day 1 over 2 hours using 0.2um in-line filter Then 500mg/m 2 iv over 1 hour every 2 weeks Premedication Dexamethasone 8mg Chlorpheniramine 10mg Ranitidine 150mg Continue until progression / unacceptable toxicity *Available via the Cancer Drug Fund Issue Date: 30 th April 2012 Page 35 of 120 Filename: MCHACPROTO Issue No: 9.0

MMC + MdG Mitomycin-C 7mg/m 2 iv day 1 repeat every 6 weeks (max 4 doses) + Folinic acid 350mg flat dose two hour infusion 5-Fluorouracil 400mg/m 2 15 minute iv bolus day 1 5-Fluorouracil 2400mg/m 2 46hr iv infusion start day 1 Repeated at 14 day intervals if MMC + Capecitabine Mitomycin-C 7mg/m 2 iv day 1 repeat every 6 weeks, max 4 doses Capecitabine 1000mg/m 2 oral bd for 14 days repeat at 21 day intervals NB see capecitabine renal function recommendations p105 if Fbc and biochemistry prior to each cycle Issue Date: 30 th April 2012 Page 36 of 120 Filename: MCHACPROTO Issue No: 9.0

Anal Carcinoma Localised squamous carcinoma of the anus Combined XRT + chemotherapy Mitomycin C 12mg/m 2 iv day 1 only (max 20mg) 5-Fluorouracil 1000mg/m 2 iv over 24hrs days 1-4 5-Fluorouracil 1000mg/m 2 iv over 24hrs daily x 4 during final week of XRT or Capecitabine 825mg/m 2 bd oral on each XRT treatment day NB see capecitabine renal function recommendations p105 if Palliative / Metastatic Cisplatin/5FU Cisplatin 60mg/m 2 iv (max 120mg) day 1 5-Fluorouracil 1g/m 2 iv over 24hrs days 1-4 or Capecitabine 1000mg/m 2 bd x 14 days Repeat at 21 day intervals max 4 courses Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Mitomycin C / Fluoropyrimidine Mitomycin C 5-Fluorouracil Capecitabine 7mg/m 2 iv day 1 repeat every 6 weeks, max 4 cycles 1000mg/m 2 iv over 24hrs days 1-4 repeat at 21 day intervals or 1000mg/m 2 bd po days 1-14 repeat at 21 day intervals if Issue Date: 30 th April 2012 Page 37 of 120 Filename: MCHACPROTO Issue No: 9.0

Gynaecological Cancer Epithelial Ovarian Cancer First Line Chemotherapy Paclitaxel/Carboplatin Paclitaxel 175mg/m 2 iv over 3 hours Carboplatin AUC 5/6 iv over 1 hour Paclitaxel premedication Chlorpheniramine 10mg Dexamethasone 16mg Ranitidine 50mg Repeat at 21 day intervals maximum 6 courses Criteria Stage Ib-IV Minimal residual disease / bulk residual disease PS 0-1 Cr Cl > 50ml/min Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if CA125 prior to each cycle or Carboplatin Carboplatin AUC 5/6 x (GFR + 25) iv at 21-28 day intervals x max 6 cycles Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if CA125 prior to each cycle Issue Date: 30 th April 2012 Page 38 of 120 Filename: MCHACPROTO Issue No: 9.0

Second line chemotherapy Relapse > 6 months post platinum Single agent carboplatin Carboplatin AUC 5-6 iv x q28 days x 4-6 cycles Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if CA125 prior to each cycle Single agent cisplatin Cisplatin 80mg/m 2 iv q 21 days x 4-6 cycles Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if CA125 prior to each cycle Paclitaxel + carboplatin See 1 st line section for doses + pre-medication schedule Repeat at 21 day intervals, max 6 doses Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if CA125 prior to each cycle Issue Date: 30 th April 2012 Page 39 of 120 Filename: MCHACPROTO Issue No: 9.0

Carboplatin + Gemcitabine Carboplatin Gemcitabine AUC4 iv at 21 day intervals 1000mg/m 2 iv days 1 and 8 of a 21 day cycle Repeat at 21 day intervals to a maximum of 6 cycles Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if CA125 prior to each cycle Carboplatin + Liposomal Doxorubicin (Caelyx ) Carboplatin Liposomal Doxorubicin (Caelyx ) AUC5 30mg/m 2 iv Repeat at 28 day intervals to a maximum of 6 cycles Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if CA125 prior to each cycle Paclitaxel 70mg/m 2 iv weekly Pre-medication Dexamethasone Chlorpheniramine Ranitidine 8mg iv before first cycle 4mg iv before second and subsequent cycles 10mg iv 50mg iv Laboratory investigations Ensure normal renal function prior to cycle 1 and repeat during subsequent cycles if clinically indicated Patients with abnormal hepatic function should be treated cautiously. Normal limits for administration apply with the exception that for patients with marrow infiltration treatment may be continued at lower platelet and neutrophil counts at treating physician discretion. Issue Date: 30 th April 2012 Page 40 of 120 Filename: MCHACPROTO Issue No: 9.0

Second / Third line chemotherapy options Paclitaxel 175mg/m 2 iv over 3hrs or 135mg/m 2 iv over 3hrs (depending on PS / prior treatment) Premedication Chlorpheniramine 10mg iv Dexamethasone 16mg iv Ranitidine 50mg iv Repeat at 21 day intervals, max 6 cycles Criteria PS 0-1 No prior taxane therapy Previous platinum Liposomal doxorubicin (Caelyx ) 40-45mg/m 2 by iv infusion initially at 1mg/min q 28 days Maximum 6 cycles Criteria PS 0-2 Platinum resistant / refractory No evidence of intestinal obstruction if CA125 prior to each cycle Topotecan 1.25mg/m 2 daily iv over 30 minutes for 5 days q 21 days 3mg/m 2 iv weekly on days 1, 8, 15 of a 28 day cycle Maximum 4 cycles Criteria PS 0-2 Platinum resistant / refractory Cr Cl > 40ml/min or if CA125 prior to each cycle Fbc prior to each dose Issue Date: 30 th April 2012 Page 41 of 120 Filename: MCHACPROTO Issue No: 9.0

Gemcitabine 1000mg /m 2 iv days 1,8,15 of a 28 day cycle. Criteria PS 0-2 Platinum resistant / refractory Reassess after 3 cycles, maximum 6 cycles if CA125 prior to each cycle Fbc prior to each dose Etoposide 50mg bd oral x 7days of 21 day cycle max 6 cycles if CA125 prior to each cycle Chlorambucil 10mg daily oral x 14 days of 28 day cycle max 6 cycles if CA125 prior to each cycle Doxorubicin 60mg/m 2 iv q21 days, max 6 cycles Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if CA125 prior to each cycle Consider LV ejection fraction if history of cardiac disease Issue Date: 30 th April 2012 Page 42 of 120 Filename: MCHACPROTO Issue No: 9.0

Epithelial Ovarian Cancer Mucinous Histology First line Carboplatin / Paclitaxel or single agent carboplatin Platinum refractory Capecitabine 1250mg/m 2 oral twice daily for 14 days NB see capecitabine renal function recommendations p105 Repeat at 21 day intervals for a maximum of 6 cycles if Fbc and creatinine prior to each cycle Capecitabine should be the treatment of choice where a central line is contra-indicated eg Failed central venous catheterisation Receiving anticoagulants but NB interaction between warfarin and capecitabine I-Cap Irinotecan 180mg/m 2 iv + atropine 600ug s/c prior to irinotecan Capecitabine 900mg/m 2 oral bd x 9 days NB see capecitabine renal function recommendations p105 Repeat at 14 day intervals Review after 12 weeks and consider continuing to 24 weeks if: SD / response. Acceptable toxicity Criteria: PS 0-1 if Fbc and creatinine prior to each cycle Issue Date: 30 th April 2012 Page 43 of 120 Filename: MCHACPROTO Issue No: 9.0

Ox-Cap Oxaliplatin 85 mg/m 2 iv day 1 Capecitabine 900mg/m 2 oral bd x 9 days NB see capecitabine renal function recommendations p105 Repeat at 14 day intervals for 6 cycles then re-assessment Avoid in patients with pre-existing neuropathy if Fbc and creatinine prior to each cycle with the exception that the lower limit for platelets for administration of Ox-Cap is 75 x 10 9 /l Endometrial Carcinoma Epithelial Advanced Doxorubicin/Cisplatin/Paclitaxel Doxorubicin 45mg/m 2 iv day 1 Cisplatin 50mg/m 2 iv day 1 Paclitaxel 160mg/m 2 iv day 2 Premedication Chlorpheniramine 10mg Dexamethasone 16mg Ranitidine 50mg Maximum of 6 cycles at 21 day intervals Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Issue Date: 30 th April 2012 Page 44 of 120 Filename: MCHACPROTO Issue No: 9.0

Mixed Mullerian Tumours Doxorubicin 75mg/m 2 iv at 21 day intervals x 6 cycles depending on response if Consider LV ejection fraction if history of cardiac disease Cisplatin Cisplatin 80mg/m 2 iv at 21 day intervals x 6 cycles or Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines or Doxorubicin/Cisplatin Doxorubicin 50mg/m 2 iv Cisplatin 50mg/m 2 iv Maximum of 6 cycles at 21 day intervals Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Consider LV ejection fraction if history of cardiac disease Issue Date: 30 th April 2012 Page 45 of 120 Filename: MCHACPROTO Issue No: 9.0

Cervical Cancer Adjuvant Not currently recommended as standard therapy Pre-XRT BMC Bleomycin 30,000 iu iv day 1 Mitomycin-C 10mg/m 2 cycles 1,3 Cisplatin 50mg/m 2 iv day 1 Repeat every 14 days for 2-4 cycles Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Advanced Squamous Carcinoma Cisplatin / Topotecan Criteria 1. >6m from completion of chemo-radiation to relapse 2. no prior radiosensitising cisplatin 3. PS 0-1 Cisplatin 50mg/m 2 iv day 1 Topotecan 0.75mg/m 2 iv days 1-3 Repeat at 21 day intervals for 4-6 cycles Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Issue Date: 30 th April 2012 Page 46 of 120 Filename: MCHACPROTO Issue No: 9.0

Paclitaxel/Cisplatin Paclitaxel Cisplatin 135mg/m 2 iv over 3 hours 50mg/m 2 iv Paclitaxel premedication Chlorpheniramine 10mg Dexamethasone 16mg Ranitidine 50mg Repeat at 21 day intervals maximum 6 courses Criteria 1. >6m from completion of chemo-radiation to relapse 2. no prior radiosensitising cisplatin 3. PS 0-1 Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Topotecan Criteria 1. PS 0-2 2. <6 months post chemoradiation 3. prior radiosensitising cisplatin Topotecan 1.2mg/m 2 (max 2mg) iv days 1-5 Repeat at 28 day intervals for 4-6 cycles Laboratory investigations Dose Modification Episode of neutropenic sepsis reduce dose for ensuing cycles by 40% Interval neutrophil count 0.5-1.0 x10 9 /l or platelets 10 50 x10 9 /l 20% reduction Interval neutrophil count <0.5x10 9 /l or platelets <10x10 9 /l 40% reduction Issue Date: 30 th April 2012 Page 47 of 120 Filename: MCHACPROTO Issue No: 9.0

Advanced Non-squamous carcinoma Paclitaxel/Cisplatin Criteria 1. >6m from completion of chemo-radiation to relapse 2. no prior radiosensitising cisplatin 3. PS 0-1 Paclitaxel Cisplatin 135mg/m 2 iv over 3 hours 50mg/m 2 iv Paclitaxel premedication Chlorpheniramine 10mg iv Dexamethasone 16mg iv Ranitidine 50mg iv Repeat at 21 day intervals maximum 6 courses Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if Paclitaxel Criteria 1. PS 0-2 2. <6 months post chemoradiation 3. prior radiosensitising cisplatin Paclitaxel 135mg/m 2 iv over 3hrs Premedication Chlorpheniramine 10mg Dexamethasone 16mg Ranitidine 50mg Repeat at 21 day intervals, max 6 cycles Issue Date: 30 th April 2012 Page 48 of 120 Filename: MCHACPROTO Issue No: 9.0

Chemo-radiotherapy schedules Criteria bulky 1B or 2B PS 0-1 Normal liver / renal / haematology (1) Cisplatin 40mg/m 2 iv (max 70mg) in 1 litre Sodium chloride 0.9% over 60min weekly x max 6 weeks 30mg/m 2 if XRT fields large Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines or (2) Cisplatin 80mg/m 2 iv day 1 5-Fluorouracil 1g/m 2 iv days 1-4 and 29-32 Laboratory investigations Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines Erythropoietin may be used to maintain haemoglobin levels during combined modality therapy in these patients. Carcinoma of the Vulva Chemoradiation Mitomycin C 12mg/m 2 (max 20mg) iv day 1 5 Fluorouracil 1000mg/m 2 iv days 1-4 and 29-32 Laboratory investigations Issue Date: 30 th April 2012 Page 49 of 120 Filename: MCHACPROTO Issue No: 9.0

Haematological Malignancies Hodgkins disease Early HD Group I Group II Group III PET/CT as part of staging Involved field XRT ABVD x 3 + IF XRT Three cycles full dose chemotherapy + IF XRT or 6 cycles full dose chemotherapy + IF XRT if residual abnormality Advanced HD Stages III / IV or I / II with mediastinal bulk + / - B symptoms ABVD Doxorubicin 25mg/m 2 iv day 1 and 15 Bleomycin 10000iu/m 2 ivday 1 and 15 Hydrocortisone 100mg iv day 1 and 15 Vinblastine 6mg/m 2 iv day1 and 15 (max 10mg) Dacarbazine 350mg/m 2 iv day 1 and 15 Repeat at 28 day intervals to CR + 2, min 6 max 8 cycles if ChlVPP Vinblastine 6mg/m 2 iv days 1 and 8 (max 10mg) Chlorambucil 6mg/m 2 po days 1-14 Prednisolone 40mg po days 1-14 Procarbazine 50mg oral tds days 1-14 Repeat 28 days from day 1 x 6 cycles) if Issue Date: 30 th April 2012 Page 50 of 120 Filename: MCHACPROTO Issue No: 9.0

Non-Hodgkins Lymphoma Low grade First line CVP-R Cyclophosphamide 600mg/m 2 iv day 1 Vincristine 1.4mg/m 2 iv day 1 (maximum 2mg) Prednisolone 50mg orally days 1-5 Rituximab 375mg/m 2 iv day 1 Repeat at 21 day intervals to a maximum of 6-8 cycles. if *Bendamustine 120mg/m 2 iv days 1 and 2 Repeat at 21 day intervals to a maximum of 8 cycles if *NB available via the Cancer Drug Fund CHOP-R Cyclophosphamide 750mg/m 2 iv day 1 Doxorubicin 50mg/m 2 iv day 1 Vincristine 1.4mg/m 2 iv day 1 Prednisolone 50mg po days 1-5 Rituximab 375mg/m 2 iv day 1 Repeat at 21 day intervals for 6 cycles Criteria: fit patients with bulky disease if Issue Date: 30 th April 2012 Page 51 of 120 Filename: MCHACPROTO Issue No: 9.0

*Maintenance Rituximab Rituximab 375mg/m 2 iv every 3 months for 2 years Criteria CR or PR following first line therapy Must commence within 2 months of completion of first line therapy *NB available via the Cancer Drug Fund Mantle Cell Lymphoma *Bendamustine 120mg/m 2 iv days 1 and 2 Repeat at 21 day intervals to a maximum of 8 cycles Criteria Option for first line therapy if *NB available via the Cancer Drug Fund Second Line *Bendamustine 120mg/m 2 iv days 1 and 2 Repeat at 21 day intervals to a maximum of 8 cycles if Criteria Unable to receive R-CHOP Unable to receive high dose therapy *NB available via the Cancer Drug Fund Issue Date: 30 th April 2012 Page 52 of 120 Filename: MCHACPROTO Issue No: 9.0

Second / third line Chlorambucil +/- Prednisolone Chlorambucil + Prednisolone 10mg daily orally for 14 days 20mg oral daily for 14 days Repeat at 28 day intervals for up to 6 cycles if Fludarabine Fludarabine 40mg/m 2 orally days 1-5 (only 3 days if heavily pre-treated) Repeat at 28 day intervals max 6 cycles Criteria Progressed after alkylating agents and anthracyclines Age < 75yrs PS 0-1 Normal marrow function NB: patients receiving fludarabine should have all blood products Irradiated if Rituximab 375mg/m 2 in 500ml Sodium chloride 0.9% iv weekly x 4 Criteria Stage III / IV follicular / Mantle cell NHL Chemoresistant (prior alkylating agent and anthracycline chemotherapy) Normal renal / hepatic function Anticipated survival > 3 months Age < 65yrs PS 0-2 Not eligible for a clinical trial Issue Date: 30 th April 2012 Page 53 of 120 Filename: MCHACPROTO Issue No: 9.0