Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non-small cell lung cancer

BACKGROUND The purpose of this study was to assess the ability of administering to patients induction chemotherapy with carboplatin and etoposide (VP-16), followed by full-course radiation therapy and weekly carboplatin with tolerable toxicity as preoperative therapy to down-stage disease thus allowing the resection of clinically staged IIIA non-small cell lung cancer. METHODS Twenty-eight eligible patients with good performance status and previously untreated, marginally resectable stage IIIA non-small cell lung cancer received induction chemotherapy with carboplatin (dosed per the Egorin formulation), and VP-16 (100 mg/m2) followed by 6000 cGy of chest radiotherapy over six weeks administered concurrently with weekly doses of 100 mg/m2 of carboplatin. Patients who had either responsive or stable disease underwent thoracotomy, with attempted surgical resection of the primary lung lesion and the areas of abnormal adenopathy. Procedures involving less than a pneumonectomy were used whenever feasible. RESULTS Fifty-two cycles of induction chemotherapy were administered. The average initial dose of carboplatin was 407 mg/m2. Toxicity was tolerable with grade 3-4 neutropenia and/or thrombocytopenia in 48 and 27% of the patients. There were no septic deaths. Full-dose radiotherapy was administered to 82% of patients, with 73% receiving at least five weekly doses of carboplatin. The radiographically assessed response rate to the neoadjuvant treatment was 64% (partial response, 46%; minimal response, 18%). Sixteen patients underwent gross tumor resection with 12 (43%) having negative 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 thoracotomy was 23 months. Eight patients were alive and in remission, with follow-up ranging from 8 to 31 months. CONCLUSIONS The authors conclude that (1) carboplatin and VP-16, followed by full-dose radiotherapy with weekly carboplatin administration, is a well tolerated and effective regimen in the treatment of patients with marginally resectable stage IIIA non-small cell lung cancer; and (2) full-course radiotherapy can be administered before surgical resection without additional surgical morbidity or mortality.