A phase i trial of bexarotene in combination with docetaxel in patients with advanced solid tumors

Background: The purpose of this study was to identify dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of docetaxel with a fixed-dose of bexarotene. Patients and Methods: This was a phase I, single-center and open-label trial of dose-escalating docetaxel with a fixed-dose oral bexarotene. Successive cohorts of 3 patients (pts), with confirmed solid tumors refractory to standard therapy or for whom no standard therapy existed, received fixed-dose oral bexarotene (400 mg/m² daily) with escalating doses of docetaxel weekly (25, 30, or 35 mg/m²) for 3 weeks on a 4-week cycle. Cohorts were expanded to 6 pts if a DLT was noted. The MTD was determined based on the occurrence of DLT in at least 2 of 6 pts during the first cycle. Results: Nineteen pts were enrolled. Seven pts were treated at 25 mg/m², 6 at 30 mg/m², and 6 at 35 mg/m² of docetaxel. The MTD for docetaxel was 30 mg/m² with 400 mg/m² of daily bexarotene. Hypothyroidism, hypertriglyceridemia, and fatigue were common toxicities. Three pts developed pulmonary toxicity (possible radiation recall pneumonitis [n = 2] and pulmonary hypertension because of tumor emboli [n = 1]). Two pts withdrew consent because of Grade 3 fatigue. Ten of 19 pts were noted to have stable disease and received more than 2 cycles of therapy. Of the 10 pts with stable disease, 5 had non-small-cell lung cancer (NSCLC), and of those 5 pts, 1 had a partial response that persisted for eight cycles. Conclusion: The MTD of docetaxel was 30mg/m² in combination with daily bexarotene at 400mg/m². Careful monitoring may be indicated in pts with previously irradiated lung tumors.