Study Of High-Dose Calcitriol Plus Docetaxel Compared With Placebo Plus Docetaxel In Androgen-Independent Prostate Cancer

Main Category: Urology / Nephrology
Also Included In: Prostate / Prostate Cancer;  Cancer / Oncology
Article Date: 20 Mar 2007 - 11:00 PDT

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UroToday.com- Calcitriol (1, 25-dihydroxycholecalciferol), the natural ligand of the vitamin D receptor, has been shown to possess antitumor activity in preclinical prostate cancer models. It is believed to exert its effect by inducing apoptosis and inhibiting proliferation, angiogenesis, and tumor invasiveness. While a phase II trial has previously shown that calcitriol may enhance the cytotoxicity of traditional chemotherapy, this had not been previously studied in a placebo-controlled fashion.

In the February 20th issue of the Journal of Clinical Oncology, Beer and colleagues from the ASCENT group (AIPC Study of Calcitriol Enhancing Taxotere) report the results of a prospective, placebo-controlled, randomized trial designed to determine whether calcitriol enhances the efficacy of docetaxel in men with androgen independent prostate cancer.

The cohort consisted of 250 men with progressive, metastatic androgen independent prostate cancer who were randomized to receive weekly docetaxel with or without DN-101, a high-dose oral formulation of calcitriol. The primary endpoint was a 50 percent reduction in PSA after 6 months; the secondary endpoint was survival.

After 6 months, only a trend was observed for an improvement in overall PSA response between the calcitriol ( 63%) and placebo groups (52%), p = 0.07. Interestingly, however, in multivariate analysis patients in the calcitriol group exhibited an improvement in overall survival after adjusting for hemoglobin and ECOG performance status, with a hazard ratio of 0.67 (95% CI 0.45 to 0.97). The estimated median survival for the calcitriol group was 24.5 months, compared with 16.4 months for the placebo group. There were no differences in the incidence of grade 3 or 4 toxicities between the treatment and placebo arms.

While this exciting industry-sponsored study was primarily designed to evaluate if adding calcitriol to docetaxel would result in a favorable PSA response, it surprisingly showed that the calcitriol/docetaxel combination was associated with a mortality risk reduction of approximately 33%. We anxiously await the results of ASCENT-2 to confirm these findings, another phase III trial comparing the efficacy of calcitriol using weekly docetaxel versus the traditional 3-weekly regimen.

Tomasz M. Beer, Christopher W. Ryan, Peter M. Venner, Daniel P. Petrylak, Gurkamal S. Chatta, J. Dean Ruether, Charles H. Redfern, Louis Fehrenbacher, Mansoor N. Saleh, David M. Waterhouse, Michael A. Carducci, Daniel Vicario, Robert Dreicer, Celestia S. Higano, Frederick R. Ahmann, Kim N. Chi, W. David Henner, Alan Arroyo, Fong W. Clow

J Clin Oncol 2007 Feb 20; 25(6):669-74.

Reviewed by UroToday.com Contributing Editor Ricardo F. Sánchez-Ortiz, MD

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