Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: the OCUU-CRPC study

• Published in: International journal of clinical oncology Vol. 25; no. 3; pp. 486 - 494
• Main Authors: Iguchi, Taro, Tamada, Satoshi, Kato, Minoru, Yasuda, Sayaka, Machida, Yuichi, Ohmachi, Tetsuji, Ishii, Keiichi, Iwata, Hiroyuki, Yamamoto, Shinji, Kanamaru, Tomohiro, Morimoto, Kazuya, Hase, Taro, Tashiro, Koichiro, Harimoto, Koji, Deguchi, Takashi, Adachi, Takahisa, Iwamoto, Katsuki, Takegaki, Yoshinori, Nakatani, Tatsuya
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.03.2020; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Androgen Antagonists - therapeutic use; Androgens; Anilides - administration & dosage; Antigens; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Castration; Flutamide; Flutamide - administration & dosage; Humans; Kallikreins - blood; Male; Medicine; Medicine & Public Health; Middle Aged; Nitriles - administration & dosage; Oncology; Original Article; Patients; Phenylthiohydantoin - administration & dosage; Phenylthiohydantoin - analogs & derivatives; Progression-Free Survival; Proportional Hazards Models; Prostate cancer; Prostate-specific antigen; Prostate-Specific Antigen - blood; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - mortality; Surgical Oncology; Survival; Tosyl Compounds - administration & dosage; Treatment Outcome; Castration-resistant prostate cancer; Flutamide; Enzalutamide; Randomized controlled trial
• ISSN: 1341-9625; 1437-7772; 1437-7772
• DOI: 10.1007/s10147-019-01554-3

Background Before the androgen target therapy era, flutamide was widely used for castration-resistant prostate cancer in Japan. Enzalutamide is currently the recommended treatment; however, the efficacy and safety of enzalutamide and flutamide after combined androgen blockade therapy with bicalutamide, has not been compared. Methods Patients with castration-resistant prostate cancer who received combined androgen blockade therapy with bicalutamide were randomly assigned to receive either enzalutamide or flutamide. The primary endpoint for efficacy was the 3-month prostate-specific antigen response rate. This trial is registered with ClinicalTrials.gov (NCT02346578) and the University hospital Medical Information Network (UMIN000016301). Results Overall, 103 patients were enrolled. The 3- (80.8% vs. 35.3%; p  < 0.001) and 6-month (73.1% vs. 31.4%; p  < 0.001) prostate-specific antigen response rates were higher in the enzalutamide than in the flutamide group. The 3-month disease progression rates (radiographic or prostate-specific antigen progression) were 6.4% and 38.8% in the enzalutamide and flutamide groups, respectively [hazard ratio (HR): 0.16; 95% confidence interval (CI): 0.05–0.47; p  < 0.001]; the 6-month rates were 11.4% and 51.1%, respectively (HR 0.22; 95% CI 0.09–0.50; p  < 0.001). Enzalutamide provided superior prostate-specific antigen progression-free survival compared with flutamide (HR 0.29; 95% CI 0.15–0.54; p  < 0.001). Median time to prostate-specific antigen progression-free survival was not reached and was 6.6 months in the enzalutamide and flutamide groups, respectively. Conclusions As an alternative anti-androgen therapy in patients with castration-resistant prostate cancer who fail bicalutamide-combined androgen blockade therapy, enzalutamide provides superior clinical outcomes compared with flutamide. Enzalutamide should be preferred over flutamide in these patients.