- This phase I study was carried out to evaluate the optimal dose of temozolomide in combination with carboplatin and paclitaxel in patients with advanced solid tumors. Patients with advanced melanoma or small cell lung cancer that could benefit from the combination of carboplatin and paclitaxel were eligible. A standard 3+3 patient cohort dose escalation design was used. Paclitaxel and carboplatin were administered at fixed doses of 175 mg/m on day 1 and an area under the curve of 5, respectively. Temozolomide was administered at a dose of 75 mg/m/day from days 2-6 and subsequent cohorts were dose escalated by 25 mg/m increments. Cycles were repeated every 28 days. The primary objective of this study was to determine the maximum tolerated dose of this combination. Fourteen patients were enrolled and 12 patients were evaluable for toxicity and response (six with melanoma and six with small cell lung cancer). The maximum tolerated dose of temozolomide was 125 mg/m, with fixed doses of carboplatin and paclitaxel. There were no treatment delays nor dose reductions at this level. There were two partial responses and two patients with stable disease in the melanoma group. Four patients had a partial response, and one had stable disease in the small cell lung cancer group. There were sustained responses in three of the four patients with melanoma who achieved a clinical benefit. In conclusion, the combination of carboplatin, paclitaxel, and temozolomide is well tolerated and warrants further study.