Herceptin (Trastuzumab) plus Capecitabine & Cisplatin (HCX) DRUG ADMINISTRATION SCHEDULE First Cycle Only: Day Drug Daily Dose Route Diluent and Rate 1 to 21 Capecitabine 625mg/m 2 Day 1 TWICE DAILY Oral Sodium Chloride 0.9% 250 ml Fast Running Furosemide 20mg ORAL Herceptin (Trastuzumab) 8mg/kg Dexamethasone 8mg Oral 250ml 0.9% NaCl over 90 minutes Ondansetron 8mg IV Oral /Slow bolus/15 min infusion Cisplatin 60 mg/m 2 IV infusion Cycles 2 to 6: Day Drug Daily Dose Route Diluent and Rate 1 to 21 Capecitabine 625mg/m 2 Day 1 TWICE DAILY Oral Sodium Chloride 0.9% 250 ml Fast Running Furosemide 20mg ORAL Herceptin (Trastuzumab) 6mg/kg Dexamethasone 8mg Oral 250ml 0.9% NaCl over 30 minutes Ondansetron 8mg Oral /Slow bolus/15 min infusion Cisplatin 60 mg/m 2 IV infusion After 6 cycles, until disease progression: Day Drug Daily Dose Route Diluent and Rate 250ml 0.9% NaCl Day 1 Herceptin 6mg/kg over 30 minutes (Trastuzumab) *Ondansetron IV must be infused over 15 minutes in patients over 65 years of age. DOSE FORM Capecitabine is supplied as 150mg and 500mg tablets, therefore calculated doses must be rounded to the nearest 150mg. HCX-protocol-CRP10-UGI0101 v1.3 Page 1 of 6
Herceptin (Trastuzumab) plus Capecitabine & Cisplatin (HCX) CYCLE LENGTH AND NUMBER OF DAYS 21 days usually for 6 cycles with chemotherapy then as single agent trastuzumab until progression APPROVED INDICATIONS First line treatment of metastatic or locally advanced inoperable gastric cancer, including tumours of the gastrooesophageal junction, who over-express HER-II (IHC 2+/FISH+ or IHC 3+ only). ELIGIABILITY CRITERIA Adenocarcinoma of stomach or gastro-oesophageal junction Inoperable locally advanced and/or metastatic disease HER2-positive tumour: IHC 3+ or ICH 2+ and FISH+ Adequate organ function and ECOG performance status 2 EXCLUSION CRITERIA Inability to swallow Capecitabine tablets Chemotherapy for advanced disease Congestive heart failure or baseline LVEF <50% Creatinine clearance <60 ml/min Requirement for oxygen therapy PREMEDICATION Adequate hydration and urinary flow is essential when administering cisplatin. Patients should be weighed (with bladder empty) prior to commencing treatment and to use 20 mg of ORAL Furosemide as a diuretic given routinely if there is no contraindication. Patient should be re-weighed at the end of cisplatin (with empty bladder) and consideration given to administering a further dose of Furosemide if weight gain is more than 1.5 Kg. RECOMMENDED TAKE HOME MEDICATION Ondansetron 8mg twice daily for 2 to 3 days Dexamethasone 4mg twice daily for 1 to 3 days Metoclopramide 10 mg three times daily as required INVESTIGATIONS / MONITORING REQUIRED FBC, U&E s and LFT s. Check renal function before commencing platinum. Use EDTA or Wright formulae to estimate GFR. GFR must be above 60ml/min for cisplatin based treatment. If GFR <60ml/min discuss with an Oncology Specialist. Prior to each cycle FBC, U&E s, LFT s as required; GFR doubled checked using Wright formulae 4 monthly: ECHO / MUGA HCX-protocol-CRP10-UGI0101 v1.3 Page 2 of 6
REVIEW BY CLINICIAN To be reviewed by either a Nurse, Pharmacist or Clinician before every cycle. NURSE / PHARMACIST LED REVIEW On cycles where not seen by clinician. ADMINISTRATION NOTES How to take: Side effects Missed dose: Post dose vomiting: Storage/ Disposal COUNSELLING POINTS FOR ORAL CAPECITABINE Take tablets 12 hours apart, within 30 minutes after the end of meal (i.e. breakfast & evening meal.) Swallow whole with water Common side effects to discuss with patient include; diarrhoea, nausea & vomiting, stomatitis (mouth ulcers), Hand-foot syndrome(painful red swelling in hands and feet), fever or infection. If patients notice any of these advise them to stop taking treatment, contact doctor/chemotherapy day unit who will take steps to manage side effects and advise on continuing treatment. If remember half an hour after they should have taken their tablets, then take the missed dose, otherwise only take the regular dose at next scheduled time. Do not double-up doses to make up for the missed doses or take extra doses at the end of the treatment cycle. In the case of vomiting within a few hours after drug intake, never repeat the administration of the dose. Tablets should be stored in cool dry place less than 30 C. Unused medicines must be returned to hospital pharmacy for disposal Advise patients of the risk of Hand-and-foot skin-reaction (Palmar/Plantar Erythrodysesthesia) and that they should stop taking capecitabine and contact the Chemotherapy Unit if they have pain, swelling, and redness of hands and/or feet. Diarrhoea is common, and may require intervention with fluids and electrolytes if severe. If diarrhoea is a problem give loperamide 2 to 4 mg four times daily as required or codeine phosphate 30mg four times daily and stop taking Capecitabine if diarrhoea moderate/severe. If palmar- plantar erythrodysesthesia is a problem could consider pyridoxine 50 mg TDS, though the clinical evidence for efficacy of this intervention is lacking. May not need to stop trastuzumab for minor hypersensitivity e.g. reactions, flushing, localised rash. Must be stopped for major reactions, e.g. hypotension, dyspnoea, angioedema or generalised urticaria. Antihistamines, paracetamol and hydrocortisone can be used to treat reactions and should be available if required but must not be used prophylatically. If patient has hypersensitivity reaction follow manufacturers re-challenge guidelines before continuing with treatment. Units administering trastuzumab must have facilities available for the treatment of anaphylaxis and resuscitation. Patients who delay treatment for more than one week should be considered for reloading (8mg/kg) of trastuzumab. HCX-protocol-CRP10-UGI0101 v1.3 Page 3 of 6
EXTRAVASATION See NECN/ Local Policy TOXICITIES Herceptin is contraindicated in patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. Risk of infusion reactions, hypersensitivity and anaphylaxis, particularly on first cycle. The majority of these events occur during or within 2.5 hours of the start of the first infusion. Pulmonary events, such as dyspnoea, bronchospasm, asthma and hypoxia. Adult Respiratory Distress Syndrome (ARDS) has been reported rarely with fatal outcome Cardiotoxicity - Do not give with anthracycline or give anthracycline within six months of patient receiving last dose of Herceptin. Chills and fevers common with first infusion Pain Myalgia, arthralgia Palmar/Plantar Erythrodysesthesia - Can be severe, patients must be forewarned Myelosuppression Nephrotoxicity due to cisplatin Nausea & Vomiting Diarrhoea Stomatitis Hyperpigmentation Alopecia Ototoxicity Neurotoxicity Metallic taste on administration Occasionally patients with heart disease may experience coronary artery spasm. DOSE MODIFICATION / TREATMENT DELAYS Haematological toxicity: Delay 1 week if WBC < 3.0, ANC < 1.5 and Platelets < 100. If ANC > 0.5 then the capecitabine may be continued at the same dose. Non-Haematological Toxicity for Oral Capecitabine Any patient with CTC toxicity should be prescribed the therapeutic option for grade 1 toxicity in addition to dose modification. HCX-protocol-CRP10-UGI0101 v1.3 Page 4 of 6
Table of dose adjustments according to CTC toxicity (Not PPE/hand/foot)) Grade 2 Grade3 Grade 4 Interrupt until resolved to Interrupt until resolved to 1 st grade 0/1, then continue at grade 0/1, then continue at Discontinue appearance 100% of original dose with 75% of original dose with treatment prophylaxis where possible prophylaxis where possible 2 nd appearance 3 rd appearance Interrupt until resolved to grade 0/1, then continue at 75% of original dose Interrupt until resolved to grade 0/1, then continue at 50% of original dose 4 th appearance Discontinue treatment Interrupt until resolved to grade0/1, then continue at 50% of original dose Discontinue treatment Table of hand/ foot toxicity grading for capecitabine only Grade Clinical Functional 1 Numbness, dysesthesia/parathesia, tingling, painless swelling or erythema Discomfort but no interruption Of normal activities 2 Discomfort which affects activities Painful erythema with swelling of daily living 3 Moist desquamation, ulceration, Blistering, severe pain Severe discomfort, unable to work or perform activities of daily living Table of Diarrhoea toxicity grading for capecitabine only CTC Toxicity % Capecitabine Grade Diarrhoea (watery Hold until recovery, then resume at 100% dose for 1 stool 2-3 times/day) remainder of course Diarrhoea (watery Hold until recovery, then resume at 75% dose for remainder 2 stool 4-6 times/day) of course Following grade 3 or 4 diarrhoea, subsequent doses of Diarrhoea (watery 3/4 Xeloda should be decreased or treatment discontinued stool >7 times/day permanently (grade 4). Renal dysfunction: Calculated Cr Clearance (ml/min) Cisplatin Capecitabine 60 100% 100% 50-59 75% 100% 45-59 75% 75% < 45 Hold cisplatin or delay with 75% < 30 additional IV fluids (consult oncologist) OMIT TREATMENT LOCATION Can be given at Cancer Centre or Cancer Units who normally treat Upper GI cancers. HCX-protocol-CRP10-UGI0101 v1.3 Page 5 of 6
REFERENCES: Findlay M et al. A Phase II study in advanced gastric cancer using epirubicin and cisplatin in combination with continuous 5-FU (ECF). Ann Oncol 1994; 5:609-616. Cunningham D et al. Capecitabine and Oxaliplatin for Advanced Esophago -gastricancer. NEJM 2008 358;1:3 6-46 Van Cutsem E et al. J Clin Oncol (Meeting Abstracts). 2009 June;27(18S):LBA4509 Document Control Document Title: HCX CNTW protocol CRP10 UGI010 Document No: Author: Approved by: CRP10 UGI010 Due for Review: June 2016 Calum Polwart, Cancer Pharmacist Nick Wadd, Consultant Oncologist Summary of Changes 1.0a First version agreed. Current 1.3 Version: Approval Signature* Date Approved: 6 June 2014 1.1a rate for cycle 1 trastuzumab amended to 90mins 1.2 Protocol reviewed. Typing errors corrected. Reloading information added. 1.3 Protocol reviewed and reissued, Antiemetic advice updated HCX-protocol-CRP10-UGI0101 v1.3 Page 6 of 6