A phase I study of docetaxel and bexarotene

Background: We conducted a single-arm, dose-escalation, phase 1 clinical trial in order to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of bexarotene in combination with docetaxel. Methods: Patients with solid tumors and no other curative treatment options were eligible. Oral bexarotene was taken daily in combination with docetaxel 25 mg/m² administered intravenously on days 1, 8, and 15 of a 28-day cycle. The dose of bexarotene started at 200 mg/m² and increased by 100 mg/m ²/dose level, until either a MTD or the final dose of 400 mg/m ² was reached. Results: Fifteen patients were enrolled in the study. Median age was 58 years. The majority had non-small-cell lung cancer. The study went to completion without reaching an MTD. Hematological toxicities were mild. Three patients developed grade 3 hypertriglyceridemia, all occurring during the first cycle of treatment. No objective responses were noted. Four patients had stable disease as a best response, 3 with non-small-cell lung cancer and 1 with angiosarcoma. Conclusions: Treatment was well tolerated and no DLT was seen at docetaxel 25 mg/m² and bexarotene 400 mg/m². Given that stable disease was durable in 4 patients, future studies with this combination may be warranted.