Randomized, phase III study of mitomycin/vindesine/cisplatin (MVP) versus weekly irinotecan/carboplatin (IC) or weekly paclitaxel/carboplatin (PC) with concurrent thoracic radiotherapy (TRT) for unresectable stage III non-small cell lung cancer (NSCLC): WJTOG0105

Abstract

7504 Background: Weekly chemotherapy with concurrent TRT displays acceptable toxicities and dependable efficacy. We conducted a randomized phase III trial to assess the efficacy and toxicity of weekly chemotherapy with concurrent TRT against MVP with concurrent TRT via a non-inferiority design. Methods: MVP: mitomycin (8 mg/m2 on days 1, 29), vindesine (3 mg/m2 on days 1, 8, 29, 36), and cisplatin (80 mg/m2 on days 1, 29) with concurrent TRT (60 Gy). Patients (pts) subsequently received 2 courses of consolidation chemotherapy with MVP; IC: weekly irinotecan (20 mg/m2)/carboplatin (AUC 2) for 6 weeks and TRT (60 Gy) followed by 2 courses of irinotecan (50 mg/m2)/carboplatin (AUC 5); PC: weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) for 6 weeks and TRT (60 Gy) followed by 2 courses of paclitaxel (200 mg/m2)/carboplatin (AUC 5). The primary endpoint was overall survival (OS), with secondary endpoints of progression free survival (PFS), response, and toxicity. Results: From Sep 2001 to Sep 2005, 456 pts were randomized. Pretreatment characteristics were well-balanced among 3 arms. Major toxicity incidences: The incidence of G3–4 neutropenia in the MVP, IC, and PC arms was 95.9, 72.1, and 46.9 % (p<0.001). The G3–4 non-hematologic toxicity incidences in terms of fatigue, febrile neutropenia, and gastrointestinal disorder were 13.0, 6.1, and 4.8 % (p<0.001), 37.0, 8.8, and 10.2 % (p<0.001), and 24.0, 8.2, and 9.5% (p<0.001) in the respective arms. The overall response rates were 66.4, 56.5, and 63.3 %, in the MVP, IC and PC arms, respectively. The median survival times were 20.5, 19.8 and 22.0 months and the median PFS (MPFS), 8.2, 8.0 and 9.5 months in MVP, IC and PC. Non-inferiority of the 2 experimental arms compared with MVP was not achieved, though no significant differences in OS and PFS were apparent among treatments. The PC arm displayed the most favorable MST, MPFS, and hematologic/non-hematologic toxicities. Conclusions: Weekly PC with TRT displays similar efficacy and more favorable toxicity profiles compared to MVP with TRT. Weekly PC with TRT warrants use as the reference regimen in forthcoming studies. [Table: see text]