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ASWCS Chemotherapy Handbook Jan 2005 Update B3 Version 2007.1 Small Cell Lung Cancer Protocols B3.1 Cisplatin-Etoposide (CE) B3.1.1 Indication • First line chemotherapy for limited small cell lung cancer when concomitant thoracic RT is planned which starts with the second cycle of chemotherapy • Prophylactic cranial radiation is given after completion of chemotherapy for patients with good response B3.1.2 Pre treatment Evaluation • Multi-disciplinary review and Histological confirmation • Investigations should include CT scan of chest, and upper abdomen, CXR • CT head scans and bone scans are performed in the event of symptoms only • Record WHO performance status, current height, weight and surface area • FBC, U&Es (including Magnesium and Calcium), Serum Creatinine, LFTs, LDH • Calculate creatinine clearance (refer to renal dose modification table) • Consider formal measurement of creatinine clearance in patients with low surface area using either 24-hour urine collection or EDTA measurements • Consider auditory assessment • Document evaluable disease where appropriate • Give adequate verbal and written information for patients and relatives concerning patient’s disease, treatment strategy and side effects/mortality risk. • Obtain written consent from patient or guardian. • If appropriate, discuss potential risk of infertility/early menopause with patient and relatives. B3.1.3 Drug Regimen Days Drug 1 Cisplatin† Dose 80mg/m² Route IV 1 and 2 100mg/m² IV Etoposide Comments IV infusion in 500ml Sodium Chloride 0.9% over 60 minutes with pre and post hydration † IV infusion in 500-1000ml Sodium Chloride 0.9% over 1 Hour †† 23/03/2007 Page 140 ASWCS Chemotherapy Handbook Jan 2005 Update 3 † †† Etoposide 200mg/m² PO Orally for 1 day only †† Refer to ASWCS Individual Drug Guidelines for specific recommendations when administering Cisplatin (Section A3.2) In patients with swallowing difficulties, Day 3 Etoposide can be given intravenously rather than orally (at a dose of 100mg/m2) B3.1.4 Additional Modifications • None B3.1.5 Dose Modifications • Dose adjustments within a cycle will be made following the guidelines shown in the following guidelines based on weekly white blood cell (WBC), absolute neutrophil count (ANC) and platelet counts, and clinical assessment of non-haematological toxicity. B3.1.5.1 Haematological • Defer therapy for 1 week if neutrophils<1.0 x 109/l or platelets < 100 x 109/l Dose modifications for subsequent cycles: • Reduce Etoposide by 25% following symptomatic neutropenia. B3.1.5.2 Renal Function GFR ml/min Cisplatin Dose Etoposide Dose > 55 Use AUC as per protocol – 100% 100% 46 – 54 Either / or Substitute with Carboplatin 85% AUC x 5 30 – 45 Cisplatin dose 80% mg=mls/min clearance † < 30 * Consider Dose Reduction 75% Carboplatin Contra-Indicated if GFR <20ml/min † Although there is experience of using the same dose of Cisplatin as the Creatinine Clearance (CrCl) (i.e. 1mg/ml/min GFR, there is no evidence to support this practice) †† If CrCl 20-30ml/min then calculate actual GFR using EDTA clearance or 24-hour urine collection and then use calculate Carboplatin dose using Calvert Equation with usual AUC B3.1.5.3 Hepatic Function Bilirubin AST/ALT (µmol/L) (µmol/L) Cisplatin Dose Etoposide Dose <26 and Normal 100% 100% 26 – 50 and <180 100% 50% 23/03/2007 Page 141 ASWCS Chemotherapy Handbook Jan 2005 Update <51 and ≥180 100% omit / 25% * 51 – 85 and Normal 100% 25% * >85 and Normal omit / delay omit / delay * The decision to treat should be confirmed by the consultant B3.1.5.4 Other Non-Haematological Dose Modifications • In case of grade 3 or 4 neurotoxicity, Cisplatin should be definitively stopped. B3.1.6 Antiemetics/supportive therapy • This regimen has moderate to severe emetic potential - refer to local protocol • Continuous Ciprofloxacin 250 mg bd and Fluconazole 50 mg od following symptomatic neutropenia • If Mucositis or Diarrhoea ≥ Grade 3 in previous course then give 66% dose of both agents B3.1.7 Cycle frequency • 21 days for up to 6 cycles B3.1.8 Adverse effects • Nausea/vomiting • Myelosuppression and risk of sepsis and thrombocytopenia • Constipation and/or diarrhoea • Alopecia • Peripheral neuropathy & ototoxicity including tinnitus • Encephalopathy • Caution with extravasation due to vesicant drugs • Nephrotoxicity • Ototoxicity • Stomatitis & Mucositis • Fatigue • Lung fibrosis • Haemorrhagic cystitis • Line thrombus 23/03/2007 Page 142 ASWCS Chemotherapy Handbook Jan 2005 Update • Electrolyte Imbalance (especially hypomagnesaemia and hypocalcalcaemia) • Hypersensitivity Reactions B3.1.9 Investigations Prior to Subsequent Cycles • Before each course check: 1. FBC 2. U&Es (including albumin & magnesium) 3. Serum Creatinine and consider formal measurement of creatinine clearance in patients with low surface area using either 24-hour urine collection or EDTA measurements. Ensure that calculated creatinine clearance >55mls/min (refer to renal dose modification table) 4. LFTs • Clinical toxicity assessment (including stomatitis, neurotoxicity & ototoxicity) B3.1.10 References • Hanna N, Bunn P, Langer C, Einhorn L, Guthrie T, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer. Journal of Clinical Oncology, 2006; 24 (13); Pg. 2038-2043 • Fukuoka M, Furuse K, Saijo N et al. Randomised trial of Cyclophosphamide, Doxorubicin and Vincristine versus Cisplatin and Etoposide versus alternation of these regimens in small-cell lung cancer. 1991. J Natl. Cancer Inst. 83: 855-61 Written By: Dr S Falk, Chemotherapy Head of Service, BHOC Authorised By: Chairman of ASWCS Network Pharmacist Group Name: Digitally signed by Mr Signature: Jarrod Dunn Mr Jarrod Dunn DN: CN = Mr Jarrod Dunn, C = GB, O = ASWCS Date: 2007.03.23 15:14:33 Z Chairman of ASWCS Network Nursing Group Name: Tariq Signature: White Date: Date: Date for review: November 2008 Digitally signed by Tariq White DN: CN = Tariq White, C = GB, O = ASWCS Date: 2007.03.23 15:14:46 Z Chairman of ASWCS Drugs & Therapeutics Committee Name: Signature: Date: Dr Steve Falk Digitally signed by Dr Steve Falk DN: CN = Dr Steve Falk, C = GB, O = ASWCS Date: 2007.03.23 15:14:56 Z 23/03/2007 Page 143