A PHASE-I STUDY OF DAILY CARBOPLATIN AND SIMULTANEOUS ACCELERATED, HYPERFRACTIONATED CHEST IRRADIATION IN PATIENTS WITH REGIONALLY INOPERABLE NONSMALL CELL LUNG-CANCER

Purpose: This Phase I study was designed to determine the maximally to lerated dose (MTD) of daily low dose carboplatin with concurrent accel erated hyperfractionated radiotherapy (AHFX) in patients with locally advanced non-small-cell lung cancer, Patients also received consolidat ion chemotherapy with carboplatin. Secondary objectives were to determ ine the response rate, response duration, sites of first relapse, and survival. Methods and Materials: Thirty patients received daily carbop latin at doses of 25 or 30 mg/m(2). Concurrent radiotherapy was given in 1.5 Gy fractions twice daily for a total dose of 60 Gy, Following c hemoradiotherapy, patients received four cycles of carboplatin at 350 mg/m(2). Results: Grade 4 esophagitis developed in 2 of 6 (33%) patien ts receiving 30 mg/m(2) of daily carboplatin and was dose Limiting, Th e remaining 24 patients received carboplatin at 25 mg/m(2), with 3 pat ients developing Grade 4 esophagitis (13%). One of 22 patients who rec eived consolidation carboplatin developed Grade 4 thrombocytopenia., A n objective response was observed in 70% of patients (2 complete and 1 7 partial). Sites of failure were local (7 patients), distant (7 patie nts), and both (3 patients). The median time to progression was 8.3 mo nths, with a median survival time of 18.3 months, The 1- and 2-year su rvival rates were 63 and 49%, respectively. Conclusions: Esophagitis w as dose Limiting when 30 mg/m(2) of daily carboplatin was administered with AHFX. At the MTD of 25 mg/m(2) of daily carboplatin plus AHFX fo llowed by four cycles of carboplatin, the regimen was shown to be safe and as active or more active than other regimens. Thus, further studi es with this regimen are warranted. (C) 1998 Elsevier Science Inc.