Effective and Safe Administration of Low-Dose Estramustine Phosphate for Castration-Resistant Prostate Cancer.

Abstract

UNLABELLED:

Despite the favorable toxicity profile at the standard dose of 560 mg daily, the tolerability and toxicology of estramustine phosphate (EMP) have been a cause for concern at administration. Moreover, we do not know whether a lower dose of 280 mg of EMP daily can be administered with some efficacy and fewer side effects. The results of our phase II study suggest that low-dose EMP is a safe treatment option with the same efficacy in patients with castration-resistant prostate cancer.

BACKGROUND:

We evaluated the efficacy and safety of low-dose estramustine phosphate (EMP) in Japanese patients with castration-resistant prostate cancer (CRPC).

PATIENTS AND METHODS:

The present study was a single-arm, nonrandomized prospective study in which all patients received EMP orally twice daily for a total dose of 280 mg/day. A total of 31 patients with CRPC were enrolled from December 2009 to December 2012 at 5 institutions in Japan. The primary endpoint was the prostate-specific antigen (PSA) response, defined as a 50% decline in the serum PSA level, confirmed ≥ 3 weeks later. The secondary endpoints included the objective response rate, interval to PSA progression, PSA response duration, progression-free survival, disease-specific survival, overall survival, safety, and quality-of-life assessment using the Functional Assessment of Cancer Therapy-Prostate scores.

RESULTS:

Ten patients (32%) had a PSA response, and no patient had an objective response. The treatment was well tolerated, and the most frequent toxicities were grade 1 to 2 nausea/vomiting, anorexia, and gynecomastia. The median interval to PSA progression was 140 days (95% confidence interval [CI], 117-260 days). The PSA response duration was 119 days (95% CI, 49-219 days). The median progression-free survival was 213 days (95% CI, 167-422 days). The 3-year disease-specific survival and overall survival rates were 68.6% (median not reached; 95% CI, 33 months to not available) and 59.9% (median 42 months, 95% CI, 28 months to not available), respectively.

CONCLUSION:

Low-dose EMP seems to be a safe treatment option with some efficacy in patients with CRPC.

• Authors: Takahiro Inoue, Keiji Ogura, Mutushi Kawakita, Hiromasa Tsukino, Shusuke Akamatsu, Toshinari Yamasaki, Yoshiyuki Matsui, Takehiko Segawa, Yoshio Sugino, Toshiyuki Kamoto, Tomomi Kamba, Shiro Tanaka, Osamu Ogawa
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 14 Issue 1 Pg. e9-e17 (Feb 2016) ISSN: 1938-0682 [Electronic] United States
• PMID: 26433627 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Hormonal
• Estramustine
• KLK3 protein, human
• Kallikreins
• Prostate-Specific Antigen

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents, Hormonal (administration & dosage)
• Disease Progression
• Estramustine (administration & dosage)
• Humans
• Kallikreins (blood)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Prospective Studies
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms, Castration-Resistant (blood, drug therapy, mortality)
• Quality of Life
• Treatment Outcome