High dose carboplatin in the treatment of lung cancer and mesothelioma: a phase I dose escalation study

Abstract

Sixteen patients with lung cancer or mesothelioma have been treated with escalating doses of carboplatin. Five patients (10 courses) were given 800 mg/m2, four patients (five courses) 1200 mg/m2 and seven patients (eight courses) 1600 mg/m2. Myelosuppression was the major toxicity encountered. The median duration of grade 4 neutropenia ranged from 1 day (800 mg/m2) to 11 days (1600 mg/m2) and the median duration of grade 4 thrombocytopenia ranged from 1 day (800 mg/m2) to 7 days (1600 mg/m2). The median fall in haemoglobin (Hb) ranged from 2.2 g/l (800 mg/m2) to 3.6 g/l (1600 mg/m2). Nephrotoxicity was encountered at all dosages and was in part, though not entirely, dose related. 2/9 patients receiving 800 mg/m2 and 4/6 of the patients receiving 1600 mg/m2 had a fall in glomerular filtration rate (GFR) greater than 25% but less than 50%. 800 mg/m2 of carboplatin was well tolerated, the performance status in 9/10 (90%) courses being 0-1 (ECOG scale). At 1600 mg/m2 in 6/8 (75%) courses the performance status was 2-4. There was one treatment-related death from neutropenia at this dose level. The severity of nausea and vomiting was not dose related but other toxicities including diarrhoea, alopecia, mild neuropathy and ototoxicity and possible CNS toxicity occurred at doses of 1200 mg/m2 and over. 5/7 patients with small cell lung cancer achieved a complete or partial response to treatment.