Acid-suppressive therapy + ketoconazole in men with CRPC
Posted Oct 07 2010 12:00am
Ketoconazole has long been used as a “third-line” agent in men with castration-resistant prostate cancer (CRPC) who have progressive disease after standard forms of hormonal therapy. For some patients, ketoconazole can be clinically effective and cost-effective compared to other clinical options.
We have also known that the addition of acid-suppressive therapy (e.g., with a drug like ranitidine/Zantac) has potentially beneficial impact on the activity of ketoconazole in men with CRPC, but there have been no published data on the clinical impact of such therapy.
Data from a new report by Keisner et al. now give us some preliminary data on the clinical effect of acid-suppressive therapy when combined with ketoconazole in the management of men with CRPC. These data are retrospective, and cannot be considered clinically definitive at the present time.
Keisner and colleagues conducted an analysis of data from 30 patients with CRPC patients treated with ketoconazole 3 times daily between January 1, 1999, and September 30, 2009. All patients had progressive disease after standard forms of androgen deprivation therapy. Here are the top-line results of this analysis:
11/30 patients had received acid-suppressive therapy (Group 1) in addition to ketoconazole and 19/30 had not (Group 2).
The average (mean) ages of the patients were 71.8 years for Group 1 and 69.6 years for Group 2.
10/11 men in Group 1 (90.9 percent) and all men in Group 2 had received antiandrogen therapy.
Only 3/11 men in Group 1 (27.3 percent) and 4/19 men in Group 2 (21.1 percent) had received antiandrogen withdrawal therapy
Median baseline PSA levels were 109.4 ng/ml for men in Group 1 and 86.9 ng/ml for men in Group 2.
Median duration of ketoconazole therapy was was 7.2 months for men in Group 1 and 5.8 months for men in Group 2.
82 percent of men in Group 1 and 100 percent of the men in Group 2 were fully adherent to their ketoconazole regimen.
For the men in Group 1, the average (median) duration of concurrent acid suppressive therapy was 3.8 months (range, 2.0 to 20.4 months).
There were differences in the PSA responses of the men in the two groups, but they were not statistically significant.
Median progression-free survival was 11.5 months for men in Group 1 as compared to 6.9 months for men in group 2. This difference was statistically significant.
This analysis by Keisner et al. suggests the possibility that adding acid-suppressive therapy to ketoconazole may be able to significantly extend the progression-free survival of CRPC patients compared to ketoconazole alone.
It would be helpful to see whether such an effect could be replicated in a small, randomized, double-blind Phase II clinical trial. It would also be interesting to know whether the addition of acid-suppressive therapy might have similar effects in combination with drugs like abiraterone acetate, given what we currently know about the mechanisms of action of these drugs.
Ketoconazole has long been used as a “third-line” agent in men with castration-resistant prostate cancer (CRPC) who have progressive disease after standard forms of hormonal therapy. For some patients, ketoconazole can be clinically effective and cost-effective compared to other clinical options.
We have also known that the addition of acid-suppressive therapy (e.g., with a drug like ranitidine/Zantac) has potentially beneficial impact on the activity of ketoconazole in men with CRPC, but there have been no published data on the clinical impact of such therapy.
Data from a new report by Keisner et al. now give us some preliminary data on the clinical effect of acid-suppressive therapy when combined with ketoconazole in the management of men with CRPC. These data are retrospective, and cannot be considered clinically definitive at the present time.
Keisner and colleagues conducted an analysis of data from 30 patients with CRPC patients treated with ketoconazole 3 times daily between January 1, 1999, and September 30, 2009. All patients had progressive disease after standard forms of androgen deprivation therapy. Here are the top-line results of this analysis:
This analysis by Keisner et al. suggests the possibility that adding acid-suppressive therapy to ketoconazole may be able to significantly extend the progression-free survival of CRPC patients compared to ketoconazole alone.
It would be helpful to see whether such an effect could be replicated in a small, randomized, double-blind Phase II clinical trial. It would also be interesting to know whether the addition of acid-suppressive therapy might have similar effects in combination with drugs like abiraterone acetate, given what we currently know about the mechanisms of action of these drugs.