Phase I/II trial of docetaxel and vinorelbine in patients with non-small cell lung cancer previously treated with platinum-based chemotherapy

We conducted a phase I/II trial of the combination of docetaxel and weekly vinorelbine in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) who were refractory or resistant to platinum-based regimens. The objectives of the study were (1) to determine the maximum tolerated doses of docetaxel and weekly vinorelbine when given in combination and (2) to evaluate the response to and quantitative and qualitative toxicity of this combination of agents. Patients were required to have an ECOG performance status of 0 or 1, evaluable lesions, and no prior treatment with docetaxel or vinorelbine. A total of 30 patients were treated on this phase I/II study. Eight patients were treated at various doses on the phase I portion of the study. Twenty-two patients (11 males, 11 females, median age 64.5 years) were treated at the phase II dose of vinorelbine 15 mg/m² weekly with docetaxel 60 mg/m² on day 1 of a 21 day cycle. Twenty of these 22 patients enrolled at the phase II dose required dose modification or delay. Sixteen patients experienced absolute neutrophil count (ANC) < 500/mm³, and eight patients had neutropenic fever. Four patients experienced partial response (18%), nine patients had stable disease (41%), and nine patients had progressive disease (41%). With a median follow-up of 11 months, median survival for these 22 patients was 15.9 months (95% CI 8.1, 23.6 months). Median time to disease progression was 3.2 months with a 95% CI of (1.4, 4.1) months. Thus, the combination of docetaxel 60 mg/m² every 3 weeks and vinorelbine 15 mg/m² weekly appears to be active as a second line regimen in NSCLC, although it is a highly myelosuppressive regimen requiring dose modification in 91% of patients.