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23 décembre 2011 5 23 /12 /décembre /2011 22:42
Nail fungus drug may slow prostate cancer progression

MedWire News : The progression of metastatic castration-resistant prostate cancer (mCPRC) may be slowed with high doses of oral itraconazole, which is more commonly used to treat fungal infections in nails, preliminary findings suggest.

Itraconazole inhibits angiogenesis, similarly to the anticancer drug bevacizamub, and disrupts the cancer-initiating Hedgehog biological pathway. Furthermore, the drug, which does not suppress adrenal androgen synthesis, has been shown to delay tumor growth in mouse prostate cancer xenograft models.

Emmanuel Antonarakis, from Johns Hopkins Hospital in Baltimore, Maryland, USA, and colleagues randomly assigned men with chemotherapy-naïve mCPRC to receive low dose (LD; 200 mg/day) or high dose (HD; 600 mg/day) itraconazole until disease progression or unacceptable toxicity.

Prostate-specific antigen (PSA) progression was defined as a 25% increase above baseline/nadir, and a 45% success rate in either arm was considered to constitute clinical significance. Non-PSA progression was clinical or radiographic progression or death without rising PSA.

In all, 29 patients were enrolled to completion in the HD arm, while the LD arm closed after enrolling 17 patients, as only two patients had stable or declining PSA levels. After median follow-up of 21.6 weeks and 11.9 weeks in the HD and LD arms, respectively, a total of 24 and 17 patients, respectively, were evaluated.

The results, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, USA, show that PSA progression-free survival (PFS) at 24 weeks was 48.4% in the HD arm and 11.8% in the LD arm, while non-PSA PFS at 24 weeks was 61.1% and 18.8%, respectively.

Median PFS was 35.9 weeks and 11.9 weeks in the HD and LD arms, respectively. PSA declines of ≥30% were observed in 28.6% of HD arm patients and 5.9% of LD arm patients, while declines of ≥50% were seen in 14.3% and 0% of patients, respectively.

Compared with baseline levels, 12 (85.7%) of 14 men from the HD arm had reduced levels of circulating tumor cells at 24 weeks. Although seven patients experienced adverse effects, such as hypokalemia, hypertension, and edema, these were amenable to treatment.

Antonarakis commented: "We also tested whether itraconazole acted as hormone therapy by tracking levels of testosterone and DHEA [dehydroepiandrosterone] in the blood, and we found no reductions of either testosterone or DHEA. This finding shows that itraconazole is not just another hormone therapy, and has a unique mechanism of action."

He added: "With these results, we believe that high-dose itraconazole is worth studying in a larger group of men with advanced prostate cancer."

By Liam Davenport

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Published by Chronimed - dans Infections froides
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