PHASE-II STUDY OF NEOADJUVANT CHEMOTHERAPY AND RADIATION-THERAPY WITHTHORACOTOMY IN THE TREATMENT OF CLINICALLY STAGED IIIA NONSMALL CELL LUNG-CANCER

Background. The purpose of this study was to assess the ability of adm inistering to patients induction chemotherapy with carboplatin and eto poside (VP-16), followed by full-course radiation therapy and weekly c arboplatin with tolerable toxicity as preoperative therapy to downstag e disease thus allowing the resection of clinically staged IIIA non-sm all cell lung cancer. Methods. Twenty-eight eligible patients with goo d performance status and previously untreated, marginally resectable s tage IIIA non-small cell lung cancer received induction chemotherapy w ith carboplatin (dosed per the Egorin formulation), and VP-16 (100 mg/ m(2)) followed by 6000 cGy of chest radiotherapy over six weeks admini stered concurrently with weekly doses of 100 mg/m(2) of carboplatin. P atients who had either responsive or stable disease underwent thoracot omy, with attempted surgical resection of the primary lung lesion and the areas of abnormal adenopathy. Procedures involving less than a pne umonectomy were used whenever feasible. Results. Fifty-two cycles of i nduction chemotherapy were administered. The average initial dose of c arboplatin was 407 mg/m(2). Toxicity was tolerable with grade 3-4 neut ropenia and/or thrombocytopenia in 48 and 27% of the patients. There w ere no septic deaths. Full-dose radiotherapy was administered to 82% o f patients, with 73% receiving at least five weekly doses of carboplat in. The radiographically assessed response rate to the neoadjuvant tre atment was 64% (partial response, 46%; minimal response, 18%). Sixteen patients underwent gross tumor resection with 12 (43%) having negativ e pathologic margins. Six patients had pneumonectomy. There were three perioperative deaths (19%); two were secondary to respiratory failure after the patients underwent a pneumonectomy. The median survival for all 28 patients was 15 months, and for the 16 patients undergoing tho racotomy was 23 months. Eight patients were alive and in remission, wi th follow-up ranging from 8 to 31 months. Conclusions. The authors con clude that (1) carboplatin and VP-16, followed by full-dose radiothera py with weekly carboplatin administration, is a well tolerated and eff ective regimen in the treatment of patients with marginally resectable stage IIIA non-small cell lung cancer; and (2) full-course radiothera py can be administered before surgical resection without additional su rgical morbidity or mortality.