Abstract
BackgroundCabazitaxel 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.MethodsCabazitaxel 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.ResultsThirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m2, 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 Cmax and AUC0–t were dose proportional for the 6–12 mg/m2 doses.ConclusionThe MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10 mg/m2. The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens.Trial registrationThe study was registered with ClinicalTrials.gov as NCT01755390.
Highlights
Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen
Promising results in preclinical studies were confirmed in early-phase clinical studies that demonstrated that cabazitaxel has a manageable toxicity profile as well as antitumour activity in a range of solid tumours, including those progressing under taxane-based therapy [8,9,10]
Cabazitaxel (25 mg/m2 once every 3 weeks) plus prednisone has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), as well as by numerous health authorities worldwide for the treatment of men with hormone refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen [12,13]
Summary
Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. Promising results in preclinical studies were confirmed in early-phase clinical studies that demonstrated that cabazitaxel has a manageable toxicity profile as well as antitumour activity in a range of solid tumours, including those progressing under taxane-based therapy [8,9,10]. Results from the pivotal Phase III trial (TROPIC; NCT00417079) demonstrated that, compared with mitoxantrone, cabazitaxel improved survival in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel [11]. Cabazitaxel (25 mg/m2 once every 3 weeks) plus prednisone has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), as well as by numerous health authorities worldwide for the treatment of men with hormone refractory metastatic prostate cancer (more recently known as mCRPC) previously treated with a docetaxel-containing regimen [12,13]. Additional dosing schedules and treatment combination regimens with cabazitaxel in a variety of tumours are being investigated
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