Combined Chemoradiotherapy Regimens of Paclitaxel and Carboplatin for Locally Advanced Non–Small-Cell Lung Cancer: A Randomized Phase II Locally Advanced Multi-Modality Protocol

PURPOSE: This phase II noncomparative randomized trial was conducted to determine the optimal sequencing and integration of paclitaxel/carboplatin with standard daily thoracic radiation therapy (TRT), in patients with locally advanced unresected stage III non-small-cell lung cancer (NSCLC). Survival data were compared with historical standard sequential chemoradiotherapy data from the Radiation Therapy Oncology Group. PATIENTS AND METHODS: Patients with unresected stages IIIA and IIIB NSCLC, with Karnofsky performance status > or = 70% and weight loss < or = 10%, received two cycles of induction paclitaxel (200 mg/m2)/carboplatin (area under the plasma concentration time curve AUC = 6) followed by TRT 63.0 Gy (arm 1, sequential) or two cycles of induction paclitaxel (200 mg/m2)/carboplatin (AUC = 6) followed by weekly paclitaxel (45 mg/m2)/carboplatin (AUC = 2) with concurrent TRT 63.0 Gy (arm 2, induction/concurrent), or weekly paclitaxel (45 mg/m2)/carboplatin (AUC = 2)/TRT (63.0 Gy) followed by two cycles of paclitaxel (200 mg/m2)/carboplatin (AUC = 6; arm 3, concurrent/consolidation). RESULTS: With a median follow-up time of 39.6 months, median overall survival was 13.0, 12.7, and 16.3 months for arms 1, 2, and 3, respectively. During induction chemotherapy, grade 3/4 granulocytopenia occurred in 32% and 38% of patients on study arms 1 and 2, respectively. The most common locoregional grade 3/4 toxicity during and after TRT was esophagitis, which was more pronounced with the administration of concurrent chemoradiotherapy on study arms 2 and 3 (19% and 28%, respectively). CONCLUSION: Concurrent weekly paclitaxel, carboplatin, and TRT followed by consolidation seems to be associated with the best outcome, although this schedule was associated with greater toxicity.