Beer TM et al. (2007) Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT investigators. J Clin Oncol 25: 669–674

Docetaxel-containing chemotherapy is the standard treatment for patients with metastatic, androgen-independent prostate cancer (AIPC). Vitamin D receptor ligands such as calcitriol have antiproliferative, proapoptotic and antiangiogenic effects that complement the cytotoxic effects of docetaxel; however, calcitriol's antineoplastic effects require intermittent, supraphysiologic dosing. Beer and colleagues, therefore, compared the safety and efficacy of high-dose oral calcitriol (DN-101) and docetaxel with that of placebo and docetaxel.

In this multicenter, double-blind trial, 250 adults with AIPC were randomly allocated to receive docetaxel plus either placebo or DN-101. Patients received 36 mg/m2 body surface area intravenous docetaxel weekly for 3 weeks (first week only 27 mg/m2) on a 4-week cycle. One day before docetaxel administration, patients received 45 µg DN-101 or placebo orally. Patients also received dexamethasone before and after docetaxel infusions. Treatment continued until progression or unacceptable toxicity occurred.

At the time of analysis (median follow-up 18.3 months), 92% of the patients had completed treatment and 49% had died. The study end point (a confirmed PSA decline of ≥50% within 6 months of enrollment) was reached by similar proportions in both treatment groups (49% placebo, 58% DN-101; overall response rates 52% and 63%, respectively). Median survival for placebo-treated patients was 16.4 months, compared with an estimated 24.5 months for DN-101-treated patients. DN-101 did not increase the toxicity of docetaxel-containing chemotherapy.

The authors suggest that adding calcitriol to docetaxel resulted in a valuable survival benefit; however, this result needs further validation.