Cisplatin / Capecitabine (+ Trastuzumab) in Gastric Cancer

Transcription

1 Cisplatin / Capecitabine (+ Trastuzumab) in Gastric Cancer Page 1 of 5 Indication: Confirmed HER2-positive (3+ or FISH+) metastatic adenocarcinoma of the stomach or gastrooesophageal junction. Patient able to tolerate and comply with oral dosage forms For Trastuzumab doses and scheduling see protocol Trastuzumab in gastric cancer Drugs/Dosage: Cisplatin 80mg/m 2 IV D1 Capecitabine 1000mg/m 2 PO twice daily from the evening of D1 to the morning of D15, followed by 7 days rest (Refer to Capecitabine dosing calculation table,appendix 1) Administration: Furosemide 40mg orally 1 litre Sodium Chloride 0.9% + 20mmol KCl + 1g Mg SO 4 IV infusion over 60 minutes Cisplatin in 1000ml Sodium Chloride 0.9% over 2 hours 1 litre Sodium Chloride 0.9% + 40mmol KCl + 1g Mg SO 4 IV infusion over 2 hours Then either 500ml Sodium Chloride 0.9% IV infusion over 60 minutes or 500ml drinking water *Follow guidance protocol for Hydration schedules & fluid balance monitoring for outpatient Cisplatin regimens Capecitabine tablets should be swallowed with water within 30 minutes after a meal. Refer to Dosing guidance table. Frequency: Main Toxicities: 3 weekly, for 6 cycles Myelosuppression; alopecia; diarrhoea; mucositis; stomatitis; nausea; vomiting; nephrotoxicity; neuropathy/ ototoxicity; cardiac disorders; coronary artery spasm; fatigue; fever; palmarplantar erythema (PPE); ovarian failure; infertility; electrolyte Anti- emetics: D1 - highly emetogenic; D2 D14 mildly emetogenic Supportive medication: Loperamide tablets 4mg stat, then 2mg prn for diarrhoea Pyridoxine tablets 50mg tds, if required for palmar-plantar erythema (PPE) Mouthwashes, when required- refer to local mouthcare guidelines Extravasation: Non-vesicant Regular investigations: FBC D1 LFTs & U&Es D1 Mg 2+ and Ca 2+ D1 EDTA Prior to 1 st cycle (if necessary) Audiogram Prior to 1 st cycle, when clinically indicated

2 Comments: Page 2 of 5 Hydration - Cisplatin Encourage oral hydration during treatment; for instance, drink a glass of water every hour during treatment, and at least a further 2 litres over the 24 hours following treatment Weight should be recorded prior to and at the end of Cisplatin treatment, and a strict fluid balance chart should be maintained. An average urine output of at least 100ml/hr must be maintained throughout treatment, and Cisplatin infusion should not be commenced unless this urine output is achieved. For low urine output, consider increasing the pre-hydration and diuretic regimen. Consider adding diuretics in weight-gain of 1.5 kg, or symptoms of fluid overload Allergy Cisplatin Anaphylactic-like reactions to Cisplatin have been reported. Facial edema, bronchoconstriction, tachycardia and hypotension may occur within minutes of Cisplatin administration. Adrenaline, corticosteroids and antihistamines have been effectively employed to alleviate symptoms. No further Cisplatin should be given unless within a desensitising protocol Electrolyte disturbances Cisplatin Disturbances in electrolytes can be a long term manifestation due to the Cisplatin induced renal tubular dysfunction. Check electrolytes- additional supplementation of magnesium, calcium or potassium may be required Fertility Both male and female patients must use contraceptive methods to prevent conception and/or reproduction during and for at least 6 months after chemotherapy Toxicities and Dose Modifications Haematological Toxicity WBC < 3.0 x 10 9 /L Or Neutrophils < 1.5 x 10 9 /L Or Platelets < 100 x 10 9 /L Delay for 1 week or until the myelosuppression is resolved. After 1 week, repeat FBC and, if normal resume treatment with full dose. - If there is a 2-week delay, give all drugs at 75% doses - If > 2 week delay, give all drugs at 50% doses Hepatic Impairment Cisplatin: No dose reduction necessary Capecitabine: In the absence of safety and efficacy data in patient with hepatic impairment, capecitabine use should be carefully monitored in patients with micro to moderate liver dysfunction. Administration of capecitabine should be interrupted if treatment-related elevations in bilirubin of >3.0 x ULN or treatment-related elevations in hepatic aminotransferases (ALT, AST) of > 2.5 x ULN occur.

3 Page 3 of 5 Renal Impairment GFR should be calculated using the Cockcroft & Gault equation in all patients; if the calculated GFR < 60 or > 120ml/min, measure EDTA clearance or creatinine clearance before prescribing. Monitor trends in serum creatinine between treatments: if 25% from baseline value, re-calculate GFR using the Cockcroft & Gault equation Cisplatin induces nephrotoxicity, which is cumulative. It is therefore contraindicated in patients with renal impairment. Consider dose reduction following the table below: CrCl (ml/min) Cisplatin Dose Capecitabine dose > 60 Give 100% Give 100% Give 75% Give 100% Give 50% 75% dose < 40 Contraindicated 75% dose < 30 Contraindicated Contra-indicated Non-Haematological Toxicities Note that severe diarrhoea and/or severe mucositis early in the first treatment cycle can be the first presenting toxicity due to DPD enzyme deficiency, in which case potentially fatal neutropenia can quickly follow. Toxicity due to capecitabine administration may be managed symptomatically and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced, it should not be increased at a later time. Doses of capecitabine omitted for toxicity are not replaced or restored. Instead the patient should resume the planned treatment cycle. Capecitabine non-haematological toxicity dosing table: Diarrhoea, abdo pain,n&v,stomatitis Immediate action Dose next cycle Grade 1 maintain dose 100% Grade 2 1 st appearance Interrupt until resolved to grade % Grade 2 2 nd appearance Interrupt until resolved to grade % Grade 2 3 rd appearance Interrupt until resolved to grade % Grade 2 4 th appearance Discontinue treatment permanently Grade 3 1 st appearance Interrupt until resolved to grade % Grade 3 2 nd appearance Interrupt until resolved to grade % Grade 3 3 rd appearance Discontinue treatment permanently Grade 4 1 st appearance Discontinue or at consultants discretion Interrupt until resolved to grade % (continues next page)

4 Page 4 of 5 Capecitabine non-haematological toxicity dosing table: Palmar-Plantar Erythema Immediate action Dose next cycle Grade 1 maintain dose 100% Grade 2 1 st appearance Interrupt until resolved to grade % Grade 2 2 nd appearance Interrupt until resolved to grade % Grade 2 3 rd appearance Discontinue treatment permanently Grade 3 1 st appearance Interrupt until resolved to grade % Grade 3 2 nd appearance Discontinue or at consultants discretion Interrupt until resolved to grade % Cardiotoxicity (Capecitabine) Coronary artery spasm is a recognised complication of capecitabine although the evidence base regarding aetiology, management & prognosis is not particularly strong. The incidence is estimated to be between 2% and 18%. Coronary artery spasm is usually reversible on discontinuing the treatment. Should a patient receiving capecitabine present with chest pains, stop the treatment. Standard investigation and treatment of angina may be required. If re-challenge is deemed necessary, this can be performed under close supervision, but should symptoms redevelop, capecitabine should be withdrawn permanently. Refer to Consultant to discuss. Neuropathy/ ototoxicity (Cisplatin) If patient develops symptoms indicative of Grade 2 Neuropathy (paresthesia interfering with function, but not interfering with activities of daily living) or Ototoxicity (tinnitus not interfering with activities of daily living), seek Consultant advice and consider changing Cisplatin to Carboplatin Drug interactions: Cisplatin -Allopurinol, colchicine, probenecid, sulfinpyrazone : increase in serum uric acid concentration -Cephalosporins, aminoglycosides, amphotericin B : increase nephrotoxic and ototoxic effects of Cisplatin in these organs -Ciclosporine : excessive immunosuppression, with risk of lymphoproliferation -Cyclizine, phenothiazines : may mask ototoxicity symptoms -Furosemide (high doses), hydralazine, diazoxide and propranolol : intensify nephrotoxicity -Oral anticoagulants : require an increased frequency of the INR monitoring -Penicillamine : may diminish the effectiveness of Cisplatin -Phenytoin : reduced epilepsy control Capecitabine -Coumarin anticoagulants-monitor INR -Phenytoin- altered plasma levels -Folinic acid- increased toxicity -Allopurinol- reduced efficacy

5 Page 5 of 5 References: NICE TA208, Nov 2010 Bang et al.(2010) Lancet; 376: Appendix 1. Table 1 Standard and reduced dose calculations according to body surface area for a starting dose of Capecitabine of 1000 mg/m 2 Dose level 1000 mg/m 2 (twice daily) Body Surface Area (m 2 ) Full dose 1000 mg/m 2 Number of 150 mg tablets and/or 500 mg tablets per administration (each administration to be given morning and evening) administration (mg) 150 mg 500 mg Reduced dose (75%) 750 mg/m 2 administration (mg) Reduced dose (50%) 500 mg/m 2 administration (mg)