Randomized Phase III Trial of Docetaxel Versus Vinorelbine or Ifosfamide in Patients With Advanced Non–Small-Cell Lung Cancer Previously Treated With Platinum-Containing Chemotherapy Regimens

TLDR

The three treatment groups were well-balanced for key patient characteristics. The study aimed to confirm phase II results of docetaxel monotherapy in advanced NSCLC patients previously treated with platinum-based chemotherapy. Three hundred seventy‑three patients were randomized to docetaxel 100 mg/m², docetaxel 75 mg/m², or vinorelbine/ifosfamide. Docetaxel yielded higher overall response rates (10.8% and 6.7% for 100 mg/m² and 75 mg/m²) and improved time to progression and 26‑week progression‑free survival versus vinorelbine/ifosfamide, with 75 mg/m² also showing a significant 1‑year survival benefit, while overall survival was similar across groups and toxicity was greatest with 100 mg/m² but acceptable with 75 mg/m².

Abstract

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non–small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m 2 (D100) or 75 mg/m 2 (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P = .001 and P = .036, respectively). Patients who received docetaxel had a longer time to progression (P = .046, by log-rank test) and a greater progression-free survival at 26 weeks (P = .005, by χ 2 test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P = .025, by χ 2 test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.