Activity of dutasteride plus ketoconazole in castration-refractory prostate cancer after progression on ketoconazole alone.
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.


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.


CONCLUSIONS
We conclude that dutasteride added to ketoconazole at the time progression might prolong time to PSA progression in patients with CRPC.
Sartor
Oliver
O
Dana-Farber Cancer Institute, Boston, MA, USA. osartor@tulane.edu
Nakabayashi
Mari
M
Taplin
Mary-Ellen
ME
Ross
Robert W
RW
Kantoff
Philip W
PW
Balk
Steven P
SP
Oh
William K
WK
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001378:Azasteroids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D000068538:Dutasteride; D006801:Humans; D007654:Ketoconazole / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
D018931:Antineoplastic Agents, Hormonal; D001378:Azasteroids; D014408:Biomarkers, Tumor; D000068538:Dutasteride; D007654:Ketoconazole