Review of two phase III randomized trials of single-agent docetaxel in previously treated advanced non--small cell...

Randomized phase III studies reported this year prove that docetaxel is superior both to best supportive care (BSC) and to a standard regimen of vinorelbine or ifosfamide as second-line therapy for advanced non--small cell lung cancer. In a landmark study authored by Dr Frances Shepherd, 204 patients with stage IIIB/IV non--small cell lung cancer who had failed previous cisplatin-based chemotherapy were randomized to receive either docetaxel (100 mg/m(2) or 75 mg/m(2) every 3 weeks) or BSC. The median survival of patients assigned to docetaxel was 7.6 months, significantly longer than the median of 4.6 months in patients treated with BSC alone. The rate of febrile neutropenia was 22% in patients receiving 100 mg/m(2) docetaxel but only 1.8% when the dose was 75 mg/m(2). Patients treated with docetaxel required less additional opioid analgesia and palliative radiotherapy than those receiving BSC. Patients in the docetaxel 75 mg/m(2) arm also were significantly less likely to lose 10% or more body weight and to experience severe fatigue. In a second phase III study led by Dr Frank Fossella, 373 patients were randomized to docetaxel 100 mg/m(2), docetaxel 75 mg/m(2), or a control arm of vinorelbine 30 mg/m(2) or ifosfamide 2 g/m(2). Median survival was similar between the two groups (range, 5.5 to 5.7 months). However, the survival rate at I year was significantly higher in patients assigned to 75 mg/m(2) than in the control arm. Patients receiving docetaxel 75 mg/m(2) experienced better global quality of life (Lung Cancer Symptom Scale: patient-rated) than patients receiving vinorelbine or ifosfamide. A higher incidence of grade 4 neutropenia and febrile neutropenia was observed in the docetaxel arms of the study, but the incidence of infections was low and nonhematologic toxicities were similar across all treatment arms. These studies show docetaxel provides meaningful survival and clinical benefits in second-line non-small cell lung cancer. The dose recommended in this setting is 75 mg/m(2) every 3 weeks.