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 >OR= 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.
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 >OR= 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.
Authors: Gregory L Branigan; Georgina Torrandell-Haro; Maira Soto; Edward P Gelmann; Francesca Vitali; Kathleen E Rodgers; Roberta Diaz Brinton Journal: Cancer Med Date: 2022-03-16 Impact factor: 4.711
Authors: Andrea Lunardi; Ugo Ala; Mirjam T Epping; Leonardo Salmena; John G Clohessy; Kaitlyn A Webster; Guocan Wang; Roberta Mazzucchelli; Maristella Bianconi; Edward C Stack; Rosina Lis; Akash Patnaik; Lewis C Cantley; Glenn Bubley; Carlos Cordon-Cardo; William L Gerald; Rodolfo Montironi; Sabina Signoretti; Massimo Loda; Caterina Nardella; Pier Paolo Pandolfi Journal: Nat Genet Date: 2013-06-02 Impact factor: 38.330