A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy

Study objective: Docetaxel has shown activity in the second-line treatment of non-small cell lung cancer (NSCLC). Phase II studies have suggested that weekly therapy with docetaxel probably has a better toxicity profile than the conventional schedule of once every 3 weeks. Our aim was to evaluate and compare the efficacy of different docetaxel schedules in NSCLC patients who did not respond to previous platinum-based chemotherapy. Setting: National teaching hospital in Taiwan. Methods: Treatment consisted of the following: (1) docetaxel, 35 mg/m² IV infusion (D₃₅) on days 1, 8, and 15 every 4 weeks; (2) docetaxel, 40 mg/m² IV (D₄₀) on days 1 and 8 every 3 weeks; and (3) docetaxel, 75 mg/m² IV (D₇₅) on day 1 every 3 weeks. Patients were randomized at a ratio of 2:2:1, with the D₇₅ arm as the control arm. From 2002 to 2004, 161 patients were enroled into the study. Results: The number of patients enrolled in each arm of the study was as follows: D₃₅ group, 64 patients; D₄₀ group, 64 patients; D₇₅ group, 33 patients. The mean ages of patients were as follows: D₃₅ group, 65 years of age; D₄₀ group, 63 years of age; D₇₅ group, 64 years of age. The median number of cycles of chemotherapy received in each group was as follows: D₃₅ group, 4; D₄₀ group, 3; D₇₅ group, 4. The objective response rates were as follows: D₃₅ group, 17.2%; D₄₀ group, 10.9%; D₇₅ group, 6.1% (p = 0.615). The major toxicity was myelosuppression. Grades 3/4 leukopenia and neutropenia were significantly higher in the D₇₅ arm of the study (p < 0.001). Drug-induced pneumonitis occurred more frequently in patients on a weekly schedule than in those on a schedule of every 3-weeks (p = 0.05). The median survival times were as follows: D₃₅ group, 8.4 months; D₄₀ group, 7.2 months; and D₇₅ group, 9.5 months (p = 0.855). The 1-year survival rates were 32.8%, 31.9%, and 28.7%, respectively. Lung cancer symptom scores showed no obvious differences among the different treatment arms, except for some minor items. Conclusions: Weekly docetaxel chemotherapy produces less myelosuppression, and better compliance and response rates than the conventional chemotherapy administered every 3 weeks. These effects were more evident in the D₃₅ group weekly schedule than in the D₄₀ weekly schedule. However, physicians should pay more attention to the possibility of a higher frequency of docetaxel-induced pneumonitis in patients receiving treatment on the weekly schedule of treatment.