Article

Phase I study of vinorelbine and paclitaxel in small-cell lung cancer

Cancer Chemotherapy and Pharmacology (impact factor: 2.83). 10/1997; 41(1):86-90. DOI:10.1007/s002800050712 pp.86-90
Source: PubMed

ABSTRACT Background: Vinorelbine and paclitaxel interfere with mitotic spindle function through different mechanisms of action. Both of the drugs
show antitumor activity in small-cell lung cancer when used as single agents; furthermore, in vitro and in vivo studies have
shown a synergistic activity between the two drugs. Patients and methods: Patients with small-cell lung cancer no longer amenable to conventional treatment were entered into a phase I study in which
vinorelbine was given at a fixed dose of 30 mg/m2 by 15-min intravenous infusion, whereas paclitaxel was given by 3-h infusion starting 1 h after vinorelbine at an initial
dose of 90 mg/m2, which was subsequently escalated by 30-mg/m2 steps. Cycles were repeated every 21 days. Results: Grade 3 neutropenia was observed only in three patients treated at the fifty dose level. Thrombocytopenia never reached
grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in three of five patients
treated at the fifth dose level (paclitaxel 210 mg/m2). Other side effects were generally mild. The overall response rate in 22 evaluable patients was 32% (95% CI 13–51%); in
particular, 1 complete response (4.5%) and 6 partial responses (27.3%) were observed. The maximally tolerated doses recommended
for phase II studies are 180 mg/m2 for paclitaxel and 30 mg/m2 for vinorelbine. The observed myelosuppression was less severe than anticipated on the basis of the effects of each drug
alone. Conclusions: The promising activity of this drug combination warrants a phase II study in untreated patients with extensive-stage small-cell
lung cancer.

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Keywords

1 complete response
 
15-min intravenous infusion
 
22 evaluable patients
 
3-h infusion
 
6 partial responses
 
different mechanisms
 
drug combination warrants
 
fifth dose level
 
fifty dose level
 
Grade 3 neutropenia
 
grade 3 peripheral neuropathy
 
grade 3. Neurotoxicity
 
mitotic spindle function
 
observed myelosuppression
 
phase II studies
 
phase II study
 
response rate
 
single agents
 
small-cell lung cancer
 
two drugs