Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall cell lung carcinoma - A modified phase I trial

BACKGROUND, A modified Phase I trial was conducted evaluating the incorpora tion of 3-dimensional conformal radiation therapy (3DCRT) into a strategy o f sequential and concurrent carboplatin/paclitaxel. in Stage III, unresecta ble nonsmall cell lung carcinoma (NSCLC). In addition, dose escalation of t horacic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was perf ormed. Endpoints included response rate, toxicity, and survival. METHODS, Twenty-nine patients with unresectable Stage In NSCLC were include d. Patients received 2 cycles of induction carboplatin (AUC 6) and paclitax el (225 mg/m(2)/3 hours) every 21 days. On Day 43, concurrent TCRT and week ly (x6) carboplatin (AUC 2) and paclitaxel (45 mg/m(2)/3 hours) was initiat ed. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts. RESULTS. The response rate to induction carboplatin/paclitaxel was 52%. Thr ee patients (10%) experienced disease progression during the induction phas e. No dose-limiting toxicity was seen during the escalation of the TCRT dos e from 60 to 74 Gy. The major toxicity was esophagitis, with 18% of patient s developing Radiation Therapy Oncology Group Grade 3 esophagitis. The over all response rate was 70% (1 complete response and 18 partial responses). S urvival rates at 1 and 2 years were 69% and 45%, with a median survival of 21 months. The 1-year progression free survival probability was 41% (95% co nfidence interval, 23-59%). CONCLUSIONS. Incorporation of 3DCRT with sequential and concurrent carbopla tin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possibl e with acceptable toxicity. Overall response and survival rates are encoura ging. Accrual is continuing in a Phase II fashion at 74 Gy with sequential and concurrent carboplatin/paclitaxel. (C) 2000 American Cancer Society.