Cisplatin100 plus Radiotherapy for locally Advanced Squamous Cell Carcinoma Head and Neck

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1 Cisplatin100 plus Radiotherapy for locally Advanced Squamous Cell Carcinoma Head and Neck Indication: 1) Concomitant chemo-radiotherapy for locally advanced squamous cell carcinoma head and neck 2) Post-operative concomitant chemo-radiotherapy for high risk locally advanced squamous cell carcinoma head and neck Regimen details: 3-weekly schedule Chemotherapy : Cisplatin 100mg/m 2 IV D1, D22, D43 (3-weekly schedule) To avoid patient requiring hospital admission, Cisplatin can be delivered as follows. See administration section for further details Cisplatin 50mg/m 2 IV D1 and D2; D22 and D23; D43 and D44 Radiotherapy (RT) : Standard fractionation : 70 Gy over 35 fractions on Mondays to Fridays, with concurrent chemotherapy from Week 1 to Week 7 4-weekly schedule Chemotherapy : Cisplatin 100mg/m2 IV D1, D29 (4-weekly schedule, moderately accelerated RT regimens) To avoid patient requiring hospital admission, Cisplatin can be delivered as follows. See administration section for further details Cisplatin 50mg/m2 IV D1 and D2; D29 and D30 Radiotherapy : Moderately accelerated fractionation : 65 Gy over 30 fractions on Mondays to Fridays, with concurrent chemotherapy from Week 1 to Week 6 Administration: (applies to 50mg/m2 ) Furosemide 40mg orally 1litre Sodium Chloride 0.9% + 20mmol KCl + 1g MgSO4 IV infusion over 60 minutes Cisplatin, in 1000ml Sodium Chloride 0.9% IV over 2 hours 1litre Sodium Chloride 0.9% + 40mmol KCl + 1g MgSO4 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 Short Hydration schedule for Cisplatin and concomitant RT Any device containing aluminium that may come in contact with Cisplatin must be avoided Frequency: 3-weekly schedule : every 21 days, for 3 cycles 4-weekly schedule : every 28 days, for 2 cycles See also Appendix 1, treatment summary on page 5 Page 1 of 5

2 Extravasation: Anti- emetics: Cisplatin: Non-vesicant Highly emetogenic - Follow local antiemetic policy Regular investigations: Laboratory tests 3-weekly schedule 4-weekly schedule FBC, Hb D1, D22, D43 and Weekly while on RT D1, D29 and Weekly while on RT LFTs & U&Es D1, D22, D43 and Weekly while on RT D1, D29 and Weekly while on RT Mg2+ and Ca2+ D1, D22, D43 D1, D29 EDTA Prior to 1 st cycle Prior to 1 st cycle Audiogram Prior to 1 st cycle Prior to 1 st cycle Comments: Haemoglobin level Radiotherapy Throughout the Radiotherapy treatment, Haemoglobin (Hb) should be maintained above 12g/dl. If the Hb falls below 12g/dl, a blood transfusion needs to be arranged (treatment may continue) 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 without Consultant approval 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 Offer assisted conception counselling (sperm banking for males) Page 2 of 5

3 DOSE MODIFICATIONS Haematological Toxicity Neutrophils Platelets Cisplatin dose 1.5 x AND 100 x Give 100% x OR x Delay chemotherapy for 1 week, continue RT. Repeat FBC If within normal parameters, resume Cisplatin at 80% dose < 1.0 x OR < 50 x Delay chemotherapy for 1 week, continue RT. Repeat FBC If within normal parameters, resume cisplatin at 60% dose 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 20% variation from baseline value, re-calculate GFR using the Cockcroft & Gault equation Cisplatin induces nephrotoxicity, which is cumulative. It is therefore contra-indicated in patients with renal impairment. Consider dose reduction following the table below: CrCl (ml/min) Cisplatin Dose > 60 Give 100% Give 80% < 50 Contraindicated. Consider Cetuximab & RT Hepatic Impairment: Cisplatin: No dose reduction necessary DOSE MODIFICATIONS FOR OTHER TOXICITIES AS APPROPRIATE PERIPHERAL NEUROPATHY / OTOTOXICITY CISPLATIN If patient develops symptoms indicative of Grade 3 neuropathy or ototoxicity, seek consultant advice and consider changing cisplatin to carboplatin AUC 5 for subsequent days of chemotherapy. Carboplatin dose should be calculated in milligrams, using the Calvert formula: Dose = Target AUC x (25 + GFR). GFR should be measured by EDTA. Grade Neuropathy-sensory Ototoxicity Cisplatin Dose 1 Paresthesia (including tingling) but not Give 100% interfering with function 2 Paresthesia interfering with function, but not interfering with activities of daily living Tinnitus not interfering with activities of daily living Give 80% 3 Paresthesia interfering with activities of daily living Tinnitus interfering with activities of daily living Consider changing cisplatin to carboplatin AUC 5. Discuss with consultant 4 Disabling Disabling Consider changing cisplatin to carboplatin AUC 5. Discuss with consultant Page 3 of 5

4 Toxicities: Drug interactions: Myelosuppression; fatigue; nausea; vomiting; constipation; diarrhoea; nephrotoxicity; neuropathy / ototoxicity; taste disturbance; electrolyte disturbances; allergic reactions; alopecia 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 References: Forastiere AA et al. N Engl J Med (2003); 349 : Jeremic B et al. JCO (2000); 18 : Pignon JP et al. Radiotherapy and Oncology (2009); 92: 4-14 Prosnitz RG et al. Int J Rad Onc Biol Phys (2005); 61: Staar S et al. Int J Rad Onc Biol Phys (2001); 50 : COIN Guidelines. October 2000 Accord Healthcare Ltd Summary of product characteristsics cisplatin. Available via [accessed 27/06/2013] Micromedex review. Cisplatin. Available via [accessed 27/06/2013] Page 4 of 5

5 Appendix 1. Treatment summary 3-weekly schedule Chemotherapy: Cisplatin 50mg/m2 IV D1 and D2; D22 and D23; D43 and D44 Radiotherapy (RT): 70 Gy over 35 fractions on Mondays to Fridays, with concurrent chemotherapy from week 1 to week 7 Week Days RT Cisplatin 4-weekly schedule Chemotherapy: Cisplatin 50mg/m2 IV D1 and D2; D29 and D30 Radiotherapy (RT): 65 Gy over 30 fractions on Mondays to Fridays, with concurrent chemotherapy from week 1 to week 6 Week Days RT Cisplatin : Give RT on that day : Give chemotherapy on that day Page 5 of 5