Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer.

Abstract

BACKGROUND:

We previously reported the pharmacokinetic profile and preliminary tolerability of cabazitaxel in a phase I study in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Here we report the final safety profile and anti-tumor activity of cabazitaxel in a larger population, including all patients enrolled in the expansion cohort of the study.

METHODS:

Japanese patients with mCRPC previously treated with docetaxel received cabazitaxel intravenously every 3 weeks plus daily prednisolone. In patients treated with the maximum tolerated dose of 25 mg/m(2) we evaluated adverse events including treatment-related neutropenia, prostate-specific antigen (PSA) response and objective response.

RESULTS:

In total, 44 patients were treated with the maximum tolerated dose. The most frequent adverse events (any grade) were neutropenia (100 %), febrile neutropenia (54.5 %), fatigue (54.5 %), nausea (52.3 %) and diarrhea (50.0 %). There were no deaths due to treatment-related adverse events. Neutropenia with prior docetaxel did not appear to influence the probability of febrile neutropenia with cabazitaxel. Most patients received therapeutic granulocyte colony-stimulating factor (G-CSF; cycle 1: 86.4 %; cycle 2 or later: 81.8 %). In the efficacy population, two of 12 patients with measurable disease had partial response (objective response rate: 16.7 %), while 10 had stable disease. PSA response rate was 29.3 % (12/41 patients). Median time to PSA progression was 3.68 months (95 % confidence interval 1.35-4.63).

CONCLUSIONS:

In this heavily pretreated Japanese population, the occurrence of neutropenia and febrile neutropenia was high, suggesting G-CSF prophylaxis may be required as part of toxicity management. However, the efficacy of cabazitaxel was consistent with global studies. ClinicalTrials.gov identifier: NCT01324583.

• Authors: Masahiro Nozawa, Hirofumi Mukai, Shunji Takahashi, Hiroji Uemura, Takeo Kosaka, Yusuke Onozawa, Jun Miyazaki, Kazuhiro Suzuki, Koji Okihara, Yoichi Arai, Tomomi Kamba, Masashi Kato, Yasutomo Nakai, Hiroshi Furuse, Haruki Kume, Hisamitsu Ide, Hiroshi Kitamura, Akira Yokomizo, Takahiro Kimura, Yoshihiko Tomita, Keiji Ohno, Yoshiyuki Kakehi
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 20 Issue 5 Pg. 1026-34 (Oct 2015) ISSN: 1437-7772 [Electronic] Japan
• PMID: 25809824 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Taxoids
• Docetaxel
• cabazitaxel

Topics

• Aged
• Antineoplastic Agents (administration & dosage, adverse effects)
• Docetaxel
• Dose-Response Relationship, Drug
• Humans
• Japan
• Male
• Middle Aged
• Prostatic Neoplasms, Castration-Resistant (drug therapy, therapy)
• Taxoids (administration & dosage, adverse effects, therapeutic use)