Phase I trial of docetaxel and vinorelbine in patients with advanced nonsmall cell lung carcinoma

BACKGROUND. With preclinical evidence of synergy, this dose-finding trialin ing the combination of docetaxel and vinorelbine given with prophylactic re ceived vinorelbine as an intravenous push immediately followed by docetaxel as a 1-hour intravenous infusion once every 2 weeks at 1 of 7 different do se levels. Vinorelbine was escalated from 15 mg/m(2) (Level I) to 45 mg/m(2 ) (LevelVII) and docetaxel was increased from 50 mg/m(2) (LeveI I) to 60 mg /m2 (Level VII). Prophylactic corticosteroids and filgrastim were employed prospectively. METHODS. Twenty-seven patients with advanced nonsmall cell lung carcinoma f ilgrastim for the treatment of patients with nonsmall cell lung carcinoma w as undertaken. RESULTS, After completion of dose Level VII, accrual was terminated because Phase II dose intensity of both agents had been reached and further escala tion was believed to be unsafe. At dose Level VII, one episode of first-cyc le febrile neutropenia and a death after three treatment cycles due to Haem ophilus influenzae sepsis (Grade 5 toxicity according to the Common Toxicit y Criteria of the National Cancer Institute) without neutropenia were noted . In all, 209 treatment cycles were administered and febrile neutropenia wa s observed in only 4 of these treatments (1.9%). Bacteremia occurred in thr ee patients (four episodes) in the absence of neutropenia. Symptomatic onyc holysis was observed in three patients. Clinically significant peripheral n europathy and fluid retention were rare. Confirmed partial responses were n oted in 10 patients for a response rate of 37% (95% confidence interval, 20 -57%). CONCLUSIONS. Docetaxel at a dose of 60 mg/m(2) and vinorelbine at a dose of 45 mg/m(2), both given every 2 weeks, can be combined safely to achieve Ph ase II dose intensity of both agents. An ongoing Phase II trial will define the activity of this treatment combination. (C) 2000 American Cancer Socie ty.