T. Giannakakis et al., Docetaxel in combination with carboplatin for the treatment of advanced non-small cell lung carcinoma: a multicentre phase I study, EUR J CANC, 36(6), 2000, pp. 742-747
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 a
dequate bone marrow, renal, liver and cardiac function, were treated with d
ocetaxel and carboplatin. Docetaxel was given at escalated doses starting f
rom 70 m/m(2) with increments of 10 mg/m(2) followed by carboplatin also ad
ministered 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 in
trapatient 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 pati
ents were assessable for toxicity. Neutropenia was the main dose-limiting t
oxicity of the regimen; overall, grade 3/4 neutropenia occurred in 16 (14%)
cycles; six (5%) neutropenic episodes were complicated with fever but ther
e 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 re
gimen for the treatment of patients with locally advanced and metastatic NS
CLC. This regimen merits further investigation in phase II trials. (C) 2000
Elsevier Science Ltd. All rights reserved.