Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours

BACKGROUND: Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. METHODS: Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5–12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. RESULTS: Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m(2), which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in C(max) and AUC(0–t) were dose proportional for the 6–12 mg/m(2) doses. CONCLUSION: The MTD of weekly cabazitaxel was 12 mg/m(2) and the recommended weekly dose was 10 mg/m(2). The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov as NCT01755390.