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/m(2) 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.