Tuesday, 12 March 2013

Itraconazole - Anti-fungal and anti-cancer

One of the common themes of this site is the use of existing drugs as anti-cancer agents. Given the many years and millions of dollars it takes to get new drugs from the lab and into early phase human trials, it makes a lot of sense to re-look at existing, approved drugs to see if they can be re-purposed as anti-cancer therapies. Prominent examples of such drugs include metformin (used in diabetes), aspirin (pain killer), beta blockers (used for treating hypertension) and mebendazole (used as an anti-parasitic agent).

The latest example is the anti-fungal drug Itraconazole. A Phase II trial has just been reported in a paper in the Oncologist - freely accessible to all here: http://theoncologist.alphamedpress.org/content/18/2/163.full. The drug was used to treat advanced prostate cancer (metastatic castration-resistant prostate cancer to be exact). Two dosing schedules were used, low-dose (200 mg/day) or high-dose (600 mg/day), and the men were treated for 24 weeks and then assessed for a reduction in PSA and, more importantly, for progression free survival.

The low dose arm of the trial was abandoned early because of the low levels of response, however the higher dose arm continued to completion. The results were fairly impressive. The primary end-point of the study was stopping the increase in PSA levels, and this was acheived in 48% of men on the high dose (12 of 25 men). The main secondary end point was freedom from disease progression (which is the more important measure overall), and here the result was that 24-week PFS rate was estimated to be 61.6%.
As the authors point out:

Importantly, the PFS duration observed here (35.9 weeks) is comparable with PFS time estimates (range, 30–40 weeks) of other FDA-approved and experimental agents in this patient population (mitoxantrone, docetaxel, tasquinimod, and cabozantinib)
The conclusion is clear that this is a drug - cheap, approved and readily available - that does have anti-cancer action for advanced prostate cancer.

In terms of next steps, the authors conclude:
Ongoing trials are now assessing the impact of itraconazole as an antineoplastic agent in patients with lung cancer, breast cancer, and basal cell carcinoma. Future studies in prostate cancer patients will compare itraconazole with placebo in men with nonmetastatic CRPC, aiming to extend the metastasis-free survival duration in this population.
And, just as important, it is yet another step in validating the use of existing drugs against cancer.

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