title: Phase I study of vinorelbine and paclitaxel in small-cell lung cancer.
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.
  
  
  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.
authors.affiliation: Istituto Medicina Interna, Università di Cagliari, Italy.
authors.forename: R V
authors.initials: RV
authors.lastname: Iaffaioli
authors.forename: G
authors.initials: G
authors.lastname: Facchini
authors.forename: A
authors.initials: A
authors.lastname: Tortoriello
authors.forename: F
authors.initials: F
authors.lastname: Caponigro
authors.forename: A
authors.initials: A
authors.lastname: Illiano
authors.forename: M
authors.initials: M
authors.lastname: Gentile
authors.forename: A
authors.initials: A
authors.lastname: Gravina
authors.forename: P
authors.initials: P
authors.lastname: Muto
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000187:drug effects; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014747:Vinblastine; D017239:Paclitaxel