A Prospective Phase II Study of Induction Carboplatin and Vinorelbine followed by Concomitant Topotecan and Accelerated Radiotherapy (ART) in Locally Advanced Non-small Cell Lung Cancer (NSCLC)

Abstract

Survival of locally advanced/unresectable non-small cell lung cancer (NSCLC) has improved with the use of concurrent radiation and chemotherapy over the past decades, but local and distant failure remain high. In addition, a key limiting factor in combining chemotherapy with accelerated radiotherapy (ART) is severe esophagitis. We investigated the toxicity, response rate, and overall survival (OS) with induction carboplatin and vinorelbine followed by concomitant topotecan and ART in patients with locally advanced/unresectable NSCLC. In this phase II trial, stage IIIA or IIIB NSCLC patients with a Karnofsky performance score >60 were eligible. Patients received induction carboplatin (area under the curve = 5.5) on days 1 and 22, and vinorelbine (25 mg/m2) on days 1, 8, 22, and 29. During the concurrent chemoradiation, patients received intravenous topotecan (0.5 mg/m2) on days 43 to 47, days 57 to 61, and days 71 to 75 before the morning radiotherapy (RT) fraction. RT was administered in an accelerated fashion at 2 Gy per fraction, twice daily for five consecutive days, every other week, to a cumulative dose of 60 Gy during a 5-week period. Thirty-seven patients were accrued; of these, 35 were evaluable. Overall response rate was 71% (14% complete response, 57% partial response). Six of 35 (17%) patients had stable disease. Four (11%) patients progressed during treatment. At a median follow-up of 45 months for surviving patients, the median survival based on Kaplan-Meier estimates is 17.9 months. OS at 1, 2, and 3 years is 62%, 41%, and 33%, respectively. Actuarial 5-year OS is 21%. The median time to first relapse is 12.2 months (9.1-24.7 months). There were no cases of grade 3 or 4 esophagitis. This combined-modality regimen yielded encouraging OS rates, with no severe esophagitis. Using four-dimensional RT treatment planning, we plan to further evaluate altered fractionation RT and chemotherapy for this group of patients.