Conventional radiation (RT) with daily carboplatin (Cb) compared to RT alone after induction chemotherapy (ICT) [vinorelbine (Vr)-cisplatine (P)]: Final results of a randomized phase III trial in stage III unresectable non small cell lung (NSCLC) cancer. Study CRG/BMS/NPC/96 of the French Lung Cancer Study Group FNCLCC and IFCT

Abstract

7016 Background: Since local failure remains frequent after RT in these patients (pts), a randomized trial was designed to assess the efficacy of concurrent daily RT-Cb given after induction chemotherapy (ICT) on local control. Method: Unresectable stage III NSCLC pts (any weight loss, WHO PS 0–2, ± supraclavicular lymph node or superior vena cava syndrom) were eligible. ICT (Vr 30 mg/m2, week (w) 1, 3, 5, and 15 mg/m2, w 2, 4, 6; P 120 mg/m2 w 1 and 5) was modified (Vr 30 mg/m2 w 1 to 9; P 100 mg/m2 w 1, 5 and 9) after 1st interim analysis (190 pts accrued) due to high incidence of metastases. CR, PR, SD pts after ICT were given RT (66 Gy, 33 fractions) with (arm B) or without (arm A) daily Cb (15 mg/m2) according to randomization performed at entry (stratification on gender, PS, histology and center). Evaluation using CT scan was performed 1 month (m) after RT, every 3 m for 3 yrs, every 6 m thereafter. To demonstrate a 10% improvement on the 1-yr local control rate, 585 pts were needed (2 interim and 1 final analysis, type I error 2.21%, type II error 20%, 2-sided logrank test). Results: From June 1996 to February 2003, 291 pts were randomized to arm A and 293 to arm B. Characteristics: mean age 60; 89% men; 94% PS 0–1; 75% non squamous in women, 40% in men. Compliance to ICT was 74–85% for Vr and 92–97% for P. Response (CR + PR) rate to ICT was 46% (initial regimen), 58% (modified regimen); 194 pts received RT alone an d 233 RT+Cb. Compliance to Cb was 97%. Median survival time was 11 and 14 m in arm A and B, respectively. In ICT responders, the 1-yr local control rate was 66 vs 72% (p=.21); it was 62 vs 70% (p=.068) in the overall population. The 3-yr metastasis incidence rate was 64 and 65% in pts given initial and modified ICT. 82% pts developed grade 3–4 toxicity, mainly uncomplicated neutropenia during ICT. 8 pts in each arm had grade 3–4 esophagitis. Toxic death was more frequent in arm B (n=21) than in arm A (n=10). Conclusion: Concurrent RT+Cb does not improve significantly the 1-y local control rate in unresectable stage III NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Pierre Fabre Oncologie