Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable Stage IIIA/B nonsmall cell lung carcinoma - A modified Phase I/II trial

BACKGROUND. A modified Phase I/II trial was conducted evaluating the incorp oration of three-dimensional conformal radiation therapy into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III unresectable nonsmall cell lung carcinoma (NSCLC. The dose of thoracic conformal radiat ion therapy (TCRT) from 60 to 74 gray (Gy) was increased. Endpoints include d response rate, toxicity, and survival. METHODS. Sixty-two patients with unresectable Stage III NSCLC were included . Patients received 2 cycles of induction carboplatin (area under the conce ntration curve [AUC], 6) and paclitaxel (225 mg/m(2) over 3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x6) carboplatin (AUC, 2) and paclitaxel (45 mg/m(2)/3 hours) were initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy). RESULTS. The response rate to induction carboplatin/paclitaxel was 40%. Eig ht patients (13%) progressed on the induction phase. No dose-limiting toxic ity was observed during the escalation of the TCRT dose from 60 to 74 Gy. T he major toxicity was esophagitis, however, only 8% developed Grade 3/4 eso phagitis using Radiation Therapy Oncology Group criteria. The overall respo nse rate was 52%. Survival rates at 1, 2, 3, and 4 years were 71%, 52%,40%, and 36%, respectively, with a median survival of 26 months. The 1-, 2-, an d 3-year progression free survival probabilities were 47%, 35%, and 29%, re spectively. CONCLUSIONS. Incorporation of TCRT with sequential and concurrent carboplat in/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encourag ing. Both locoregional and distant failure remain problematic in this popul ation of patients. (C) 2001 American Cancer Society.