A phase I study of daily carboplatin and simultaneous accelerated, hyperfractionated chest irradiation in patients with regionally inoperable non-small cell lung cancer.

PURPOSE

This Phase I study was designed to determine the maximally tolerated dose (MTD) of daily low dose carboplatin with concurrent accelerated hyperfractionated radiotherapy (AHFX) in patients with locally advanced non-small-cell lung cancer. Patients also received consolidation chemotherapy with carboplatin. Secondary objectives were to determine the response rate, response duration, sites of first relapse, and survival.

METHODS AND MATERIALS

Thirty patients received daily carboplatin at doses of 25 or 30 mg/m2. Concurrent radiotherapy was given in 1.5 Gy fractions twice daily for a total dose of 60 Gy. Following chemoradiotherapy, patients received four cycles of carboplatin at 350 mg/m2.

RESULTS

Grade 4 esophagitis developed in 2 of 6 (33%) patients receiving 30 mg/m2 of daily carboplatin and was dose limiting. The remaining 24 patients received carboplatin at 25 mg/m2, with 3 patients developing Grade 4 esophagitis (13%). One of 22 patients who received consolidation carboplatin developed Grade 4 thrombocytopenia. An objective response was observed in 70% of patients (2 complete and 17 partial). Sites of failure were local (7 patients), distant (7 patients), and both (3 patients). The median time to progression was 8.3 months, with a median survival time of 18.3 months. The 1- and 2-year survival rates were 63 and 49%, respectively.

CONCLUSIONS

Esophagitis was dose limiting when 30 mg/m2 of daily carboplatin was administered with AHFX. At the MTD of 25 mg/m2 of daily carboplatin plus AHFX followed by four cycles of carboplatin, the regimen was shown to be safe and as active or more active than other regimens. Thus, further studies with this regimen are warranted.