Randomized phase III trial of docetaxel and cisplatin combination chemotherapy versus mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer: OLCSG 0007

Abstract

7515 Background: Two groups in the US and Japan have demonstrated the superiority of cisplatin-based second-generation chemotherapy with concurrent thoracic radiation therapy (TRT) over sequential TRT in locally advanced non-small-cell lung cancer (LA-NSCLC). In our phase I/II trial, docetaxel and cisplatin (DP) chemotherapy with concurrent TRT gave a favorable response and survival (BJC 89, 2003). A phase III, randomized trial was conducted to assess the efficacy and safety of DP chemotherapy with concurrent TRT. Methods: Patients with LA-NSCLC were randomly assigned to two arms, according to stratification by performance status (PS, 0 versus 1), stage (IIIA versus IIIB), and institution. Chemotherapy consisted of docetaxel 40 mg/m2 and cisplatin 40 mg/m2 on days 1, 8, 29, and 36 in the DP arm, and mitomycin 8 mg/m2 and cisplatin 80 mg/m2 on days 1 and 29, and vindesine 3 mg/m2 on days 1, 8, 29, and 36 in the MVP arm. In both groups, TRT began on day 1 (2 Gy/5 fractions/week; total 60 Gy, no split). Results: Between July 2000 and July 2005, 200 patients entered the trial at 17 institutes in Japan. The table below summarizes patient characteristics and the results. At 2 years, the survival rate was significantly higher in the DP arm than in the MVP arm (stratified Wilcoxon test). Hematological toxicities and febrile neutropenia were significantly higher in the MVP arm than in the DP arm. No significant difference was observed in non-hematological toxicities. Treatment-related deaths occurred in the MVP arm (one pneumonia+pneumothorax) and in the DP arm (two radiation pneumonitis, one sepsis). Conclusions: The trial met the primary endpoint (2-year survival rate). In LA-NSCLC, DP chemotherapy was effective and had acceptable toxicity compared with cisplatin-based second-generation chemotherapy combined with concurrent TRT. Characteristics/Results MVP arm DP arm Number of randomized patients 101 99 Median age (range) 64 (34–75) 65 (40–75) Gender male/female 88/13 92/7 Performance status 0/1 50/51 46/53 Stage IIIA/IIIB 33/68 33/66 Overall response rate: CR+PR, % (95% CI) 70.3 (60.4–79.0) 78.8 (69.4–86.4) Median survival time, months (95% CI) 23.7 (15.9–33.2) 26.8 (23.6–33.4) 2-yr survival rate, % (95% CI) 48.1 (38.0–57.5)* 60.3 (49.9–69.2)* 5-yr survival rate, % (95% CI) 16.6 (8.0–28.0) 23.5 (13.8–34.7) * p = 0.0183 (crude 0.0251) by stratified Wilcoxon test; p = 0.0588 (crude 0.0419) by stratified log-rank test; CI, confidence interval. No significant financial relationships to disclose.