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Clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer.

ABSTRACT: Castration resistant prostate cancer has historically been considered chemotherapy insensitive. However, the approval of estramustine phosphate, mitoxantrone, and docetaxel, over the past few decades, has challenged this notion. Despite these advances, until recently, only docetaxel had been shown to improve survival in patients with castration-resistant disease, and there has been no standard treatment options available for men with disease progression on docetaxel. In the last year, cabazitaxel, a novel taxane with decreased affinity for ATP-dependent drug efflux pump P-glycoprotein, became the first cytotoxic agent to demonstrate an improvement in survival in men with docetaxel-refractory disease, and has received regulatory approval for treatment in this setting. In this review, we examine the clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer, as well as rationale and direction of future therapeutic investigation.

SUBMITTER: Tsao CK

PROVIDER: S-EPMC3117627 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer.

Tsao Che-Kai CK Seng Sonia S Oh William K WK Galsky Matthew D MD

Clinical Medicine Insights. Oncology 20110524

Castration resistant prostate cancer has historically been considered chemotherapy insensitive. However, the approval of estramustine phosphate, mitoxantrone, and docetaxel, over the past few decades, has challenged this notion. Despite these advances, until recently, only docetaxel had been shown to improve survival in patients with castration-resistant disease, and there has been no standard treatment options available for men with disease progression on docetaxel. In the last year, cabazitaxe ...[more]

PMID: 21695098

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Project description:Background:Several studies have reported the efficacy of cabazitaxel in cancer therapy; however, investigations of its safety are few. The aim of this study was to retrospectively analyze the efficacy and safety of cabazitaxel based on treatment outcome data. Methods:A questionnaire form on the use of cabazitaxel was mailed to hospitals associated with the Shinshu University. Responses were received from 11 institutions regarding 55 cases. Results:Patients received a median of 4 courses of cabazitaxel treatment. Decreases in prostrate-specific antigen (PSA) were observed in 61.5% of cases with declines of 30%, 50%, and 90% in 36.5%, 23.0%, and 7.6% of cases, respectively. PSA progression-free survival was 5.0 months, and overall survival after the start of cabazitaxel was 13.0 months. Forty-five patients received postcabazitaxel treatment; 17 showed decreased PSA. Safety assessment indicated that white blood cell and neutrophil counts were significantly higher in the second than in the first course of treatment and Grade 3 to 4 leukopenia and neutropenia significantly decreased. Twenty-four subjects were aged ?75 years; 79% of them had their doses reduced at the first administration. The mean dose was 20 mg/m2. However, there was no significant difference in the PSA progression-free survival between the ?75-year-old and <75-year-old groups. Patients in the ?75-year-old group, particularly those whose doses were not reduced, experienced several Grade 3 to 4 adverse effects. Ten patients discontinued treatment owing to adverse effects and systemic worsening. Conclusions:To use cabazitaxel effectively, starting administration as early as possible before disease progression is important, and even if Grade 3 to 4 leukopenia and neutropenia are observed during the first course, it is important to carefully maintain the dose. Even when treating elderly patients, reducing the dose does not reduce therapeutic efficacy. However, because this cohort experienced several ? Grade 3 adverse effects, a great deal of caution is required.

Dataset Information

Clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer.

Publications

Clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer.

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