PREOPERATIVE CHEMOTHERAPY FOLLOWED BY CONCURRENT CHEMORADIATION THERAPY BASED ON HYPERFRACTIONATED ACCELERATED RADIOTHERAPY AND DEFINITIVE SURGERY IN LOCALLY ADVANCED NON-SMALL-CELL LUNG-CANCER - MATURE RESULTS OF A PHASE-II TRIAL

Purpose: To evaluate the feasibility and efficacy of an intensive mult imodality approach with combination chemotherapy, hyperfractionated ac celerated chemoradiotherapy, and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer s tages IIIA and IIIB (LAD-NSCLC).Patients and Methods: Following stagin g, including mediastinoscopy, 94 patients with inoperable LAD-NSCLC we re treated preoperatively with chemotherapy (three courses of split-do se cisplatin and etoposide [PE]) followed by concurrent chemoradiother apy (one course of PE combined with 45 Gy hyperfractionated accelerate d radiotherapy). After repeat mediastinoscopy, patients underwent surg ery 4 weeks postradiation. Results: Of 94 consecutive patients (52 sta ge IIIA [greater than or equal to two lymph node levels involved] and 42 stage IIIB [no pleural effusion, no supraclavicular nodes]), 62 (66 %) completed induction and underwent surgery Complete resection (RO) w as achieved in 50 (53% of all patients) and pathologic complete respon se (PCR) in 24 (26%). After a median follow-up of 43 months, the media n survival time was 20 months for IIIA, 18 months for IIIB, and 42 mon ths for RO patients. Calculated survival rates at 4 years were 31%, 26 %, and 46%. Two patients died of sepsis preoperatively and four died p ostoperatively of pleural empyema (n = 1), stump insufficiency (n = 2) , and cardiac failure (n = 1). Other toxicities were accept able-mainl y hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy. Conclusion: This intensive multimodality tr eatment is feasible and demonstrates high efficacy in prognostically u nfavorable LAD-NSCLC subgroups with high RO rates and improved long-te rm survival compared with historical controls. (C) 1998 by American So ciety of Clinical Oncology.