Docetaxel in combination with carboplatin for the treatment of advanced non-small cell lung carcinoma: a multicentre phase I study

Docetaxel and carboplatin have shown in vitro and in vitro activity against non-small cell lung cancer (NSCLC). A phase I study was conducted in order to determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) or their combination. Chemotherapy-naive patients with stags IIIB and IV NSCLC, age < 75 years old, performance status (WHO) 0-2. with adequate bone marrow, renal, liver and cardiac function, were treated with docetaxel and carboplatin. Docetaxel was given at escalated doses starting from 70 m/m(2) with increments of 10 mg/m(2) followed by carboplatin also administered at escalated doses starting from AUC 5 to 7 AUC (mg/ml.min); the regimen was administered every 3 weeks. No colony-stimulating factor or intrapatient escalation was allowed. The toxicity of the regimen was assessed during the first chemotherapy cycle. 35 enrolled patients received a total of 114 chemotherapy cycles (median 3 cycles/patient: range: 1-8). All patients were assessable for toxicity. Neutropenia was the main dose-limiting toxicity of the regimen; overall, grade 3/4 neutropenia occurred in 16 (14%) cycles; six (5%) neutropenic episodes were complicated with fever but there was no septic death. Grade 3/4 thrombocytopenia was uncommon (two cycles; 2%). Grade 3/4 diarrhoea occurred in 5 (14%) patients whilst neurotoxicity, fatigue and mucositis were extremely uncommon. Two MTDs were defined: the MTD1 was docetaxel 80 mg/m(2) and carboplatin AUC 7 mg/ml.min whilst MTD2 was docetaxel 100 mg/m(2) and carboplatin AUC 6 mg/ml.min. The combination of docetaxel and carboplatin is a feasible and well-tolerated outpatient regimen for the treatment of patients with locally advanced and metastatic NSCLC. This regimen merits further investigation in phase II trials. (C) 2000 Elsevier Science Ltd. All rights reserved.