Preliminary data on itraconazole in treatment of mCRPC

Preliminary data from a Phase II clinical trial have suggested that the antifungal drug itraconazole, when used at high dose levels, may have clinical benefit in the treatment of metastatic, castration-resistant prostate cancer (mCRPC). However, whether can be as effective as drugs like abiraterone, MDV3100, and TAK-700 is not known at this time, and it does have cardiovascular side effects that could be a real problem.

Antonarakis et al. will present data from their Phase II clinical trial in a poster at the annual meeting of the American Society of Clinical Oncology (ASCO) this afternoon, and additional information is available in a media release from Johns Hopkins.

The bottom line is that itraconazole therapy — when used at a dose of 600 mg/day — does seem to be able to delay time to progression and lower PSA levels by 30 percent or more in a significant proportion of men with mCRPC. However, there was a range of toxicities associated with the use of itraconazole in this study, and the common ones included fatigue, nausea, anorexia, rash, and hypokalemia/hypertension/edema. There was no sign of heart failure in patients in this study, but this is a known adverse effect associated with itraconazole therapy.

Antonarakis and his colleagues emphasize that, at this time, itraconazole needs further study before it should be considered as being an effective or safe treatment for men with mCRPC.

2 Responses

  1. Thanks for reporting this most interesting research!

    While the study was small, the strong success signal from the primary and secondary results is promising for this agent that is new to prostate cancer though apparently already approved for fungal infections (as was ketoconazole).

    I’m especially interested in how it compares with ketoconazole, which appears to be the antiandrogen preferred by some well-known doctors with practices specializing in prostate cancer who use it in second-line hormonal blockade after Casodex (bicalutamide) has failed as the second element in the triple hormonal blockade approach (LHRH agonist, or perhaps LHRH agonist recently as an option; antiandrogen, with bicalutamide typically used for first line blockade; and a 5-alpha-reductase inhibitor, either Avodart or finasteride). They have reported great success with ketoconazole and have found out how to manage its numerous drug interactions and side effects for many of their patients. I’m thinking the same success will be achieved with itraconazole if it is adopted.

    The poster abstract explains that 30% of the patients had been pre-treated with ketoconazole. I’m wondering if this was as the second element of triple blockade or a stand-alone. I suspect it was the latter. Any insight on that? The abstract does not report results for the patients who had been pre-treated with ketoconazole. I’m wondering if the researchers have tracked that data and whether they intend to formally report it.

    This is not an academic interest for me as I am now at the 11.5-year point since starting hormonal blockade as my sole therapy. It evolved to triple blockade in my first year, and I was able to go on intermittent therapy despite starting out with a challenging case. (My bPSA was 113.6, GS 4 + 3 = 7 (Epstein), all cores positive, most 100% cancer, perineural invasion, stage 3 [“rock hard” prostate], but scans surprisingly negative [bone, CT, ProstaScint at Johns Hopkins].) In my first two cycles I was on full therapy for a total of 50 months and on vacation (maintenance therapy) for a total of 55 months. During my third cycle I was on full therapy for 19 months and have been on vacation for 13 months, but about to start low-dose thalidomide again to extend the vacation period, as I did at the tail of the first two vacation periods. At the moment, except for a serious case of prostate cancer, I am very healthy and am free of any apparent symptoms or side effects of treatment, leading a normal life as I approach my 68th birthday.

  2. Jim: All that I know at this time is what appears in the ASCO abstract and the related media release from Johns Hopkins referred to above.

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