Preoperative chemotherapy (cisplatin and fluorouracil) and radiation therapy in stage III non-small cell lung cancer: A phase 2 study of the LCSG

Study objective: To determine the feasibility, toxicity, and potential efficacy of neoadjuvant chemoradiotherapy before surgery in patients with non-small cell lung cancer limited to the chest. Design: Phase 2 pilot study. Setting: Multi-institutional, multimodality cooperative group. Patients: Eight-five patients with advanced stage III-A or minimal stage III-B non- small cell lung cancer in whom attempted resection would have been likely to leave residual disease. Intervention: Cisplatin, 75 mg/m², was given on days 1 and 29; fluorouracil, 1 g/m² for 24 h, was given as a continuous infusion on days 1 to 4 and 29 to 32; thoracic radiation, 30 Gy in 15 fractions, was administered on days 1 to 19. Thoracotomy with tumor resection was planned for day 57. Measurements and results: Two patients achieved a complete and 46 achieved a partial response after the neoadjuvant chemoradiotherapy for an overall response rate of 56%. Toxicity was moderate but acceptable. Fifty- four patients underwent thoracotomy and tumor resection was attempted in 44; 29 (34%) had complete and 15 (18%) had incomplete resections. There was no apparent increase in postoperative complications. In eight patients (9%), no viable tumor was detected pathologically in the resection specimen. Of the 18 patients whose tumors were completely resected and had disease recurrence, none had recurrence only in the chest, 15 (83%) had recurrence in distal sites, and 3 (17%) developed second primary tumors. Median survival of all patients was 13 months. Conclusions: This neoadjuvant regimen did not appear to provide major benefit in patients with advanced but potentially resectable non-small cell lung cancer. Further studies are needed to better define the relative roles of preoperative radiotherapy and chemotherapy.