Activity of Dutasteride Plus Ketoconazole in Castration-Refractory Prostate Cancer After Progression on Ketoconazole Alone

作者：Sartor Oliver^*; Nakabayashi Mari; Taplin Mary Ellen; Ross Robert W; Kantoff Philip W; Balk Steven P; Oh William K

来源：Clinical Genitourinary Cancer, 2009, 7(3): E90-E92.

DOI：10.3816/CGC.2009.n.030

• 5-alpha reductase
• Androgen receptor
• Dihydrotestosterone
• Prostate-specific antigen

Background: Ketoconazole is a commonly used secondary hormonal therapy in castration-refractory prostate cancer (CRPC), but disease progression inevitably occurs. Both prostatic and metastatic lesions in patients with CRPC overexpress 5-alpha reductase (SRDA5) type I. We hypothesized that SRDA5 inhibition in combination with ketoconazole would mitigate progression after treatment with ketoconazole alone. Patients and Methods: A total of 10 patients with CRPC with progression after ketoconazole treatment were treated with a combination of ketoconazole plus dutasteride 0.5 mg/day, a dual SRDA5 inhibitor. Results: After dutasteride addition, 8 (80%) of the 10 patients had varying degrees of prostate-specific antigen (PSA) decline relative to baseline. Median progression-free survival after dutasteride addition was 4.9 months (range, 2.7 + to 9.8 months); no patient had a >= 50% PSA decline. Conclusion: We conclude that dutasteride added to ketoconazole at the time progression might prolong time to PSA progression in patients with CRPC.

• 出版日期2009-10