Background: Cabazitaxel (CBZ), a novel taxoid agent, promotes tubulin assembly and stabilizes microtubules, as docetaxel (DTX). CBZ had antitumor activity in DTX-resistant tumor models in vitro. We assessed dose-limiting toxicities (DLTs), safety and efficacy of CBZ in patients (pts) with mCRPC with prior DTX treatment. Methods: This was an open-label, dose escalation study of CBZ every 3 weeks, with daily prednisolone. Two CBZ dose levels (20 or 25 mg/m²) were set in the dose escalation cohort to determine the maximum tolerated dose (MTD). Pts in the expansion cohort received the MTD. DLTs were evaluated at cycle 1 and were defined as follows: Grade (Gr) 4 neutropenia > 7 days, Gr 4 thrombocytopenia, Gr 4 febrile neutropenia (FN), or Gr 3/4 non-hematological toxicities. Gr 3/4 neutropenia was prospectively studied based on occurrence of Gr 3/4 neutropenia during prior DTX treatment. Results: A total of 48 pts received CBZ (median age 66.1 years; ECOG PS: 0, 34 pts; 1, 14 pts; median cumulative DTX dose 753 mg/m²). None of the evaluable pts in the dose escalation cohort experienced a DLT. All pts had at least one Gr 3/4 adverse event (AE). Frequent Gr 3/4 AEs at 25 mg/m² were neutropenia (44 pts, 100%) and FN (24 pts, 54.5%). G-CSF prophylaxis was not allowed at cycle 1 and was only used in 10% of cycles from cycle 2 onward. Neutropenia occurrence during prior DTX treatment did not affect neutropenia or FN incidence during CBZ treatment. No pt discontinued CBZ due to neutropenia or FN and no toxic death was reported. In total, 12/41 pts (29.3%) had a PSA response, and 2/12 evaluable pts had a partial response as the best overall response. Conclusions: The safety profile of CBZ in Japanese pts was generally consistent with that reported in previous studies. The cumulative dose of prior DTX was higher and use of G-CSF prophylaxis less frequent than in previous studies, which may have contributed to the increased incidence of neutropenia and FN in Japanese pts. The majority of neutropenia and FN events were manageable and did not lead to treatment discontinuation. In terms of safety and efficacy, CBZ has a favourable risk–benefit profile in Japanese pts with mCRPC following prior DTX therapy. Clinical trial information: NCT01324583.