Journal of Clinical Oncology, Vol 16, 622-634, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

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

W Eberhardt, H Wilke, G Stamatis, M Stuschke, A Harstrick, H Menker, B Krause, MR Mueller, M Stahl, M Flasshove, V Budach, D Greschuchna, N Konietzko, H Sack and S Seeber
Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen Medical School, Essen-Heidhausen, Germany. wilfried.eberhardt@uni-essen.de

PURPOSE: To evaluate the feasibility and efficacy of an intensive multimodality approach with combination chemotherapy, hyperfractionated accelerated chemoradiotherapy, and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer stages IIIA and IIIB (LAD-NSCLC). PATIENTS AND METHODS: Following staging, including mediastinoscopy, 94 patients with inoperable LAD- NSCLC were treated preoperatively with chemotherapy (three courses of split-dose cisplatin and etoposide [PE]) followed by concurrent chemoradiotherapy (one course of PE combined with 45 Gy hyperfractionated accelerated radiotherapy). After repeat mediastinoscopy, patients underwent surgery 4 weeks postradiation. RESULTS: Of 94 consecutive patients (52 stage IIIA [> or = two lymph node levels involved] and 42 stage IIIB [no pleural effusion, no supraclavicular nodes]), 62 (66%) completed induction and underwent surgery. Complete resection (R0) was achieved in 50 (53% of all patients) and pathologic complete response (PCR) in 24 (26%). After a median follow-up of 43 months, the median survival time was 20 months for IIIA, 18 months for IIIB, and 42 months for R0 patients. Calculated survival rates at 4 years were 31%, 26%, and 46%. Two patients died of sepsis preoperatively and four died postoperatively of pleural empyema (n = 1), stump insufficiency (n = 2), and cardiac failure (n = 1). Other toxicities were acceptable-mainly hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy. CONCLUSION: This intensive multimodality treatment is feasible and demonstrates high efficacy in prognostically unfavorable LAD-NSCLC subgroups with high R0 rates and improved long-term survival compared with historical controls

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