The addition of high-dose calcitriol(Drug information on calcitriol) (the active form of vitamin D) to weekly treatment with docetaxel(Drug information on docetaxel) (Taxotere) appears to improve response in men with hormone-refractory prostate cancer without compromising safety, according to the results of a study reported at the 38th annual meeting of the American Society of Clinical Oncology (ASCO).
Data from a phase II clinical trial suggest the efficacy of the docetaxel/calcitriol combination almost doubles compared to docetaxel alone, as measured by prostate-specific antigen (PSA) response rate. The study showed that 81% of patients treated with the combination decreased their PSA levels by more than half. Studies of docetaxel without calcitriol have reported a 42% overall PSA response rate.
"Because there is no standard treatment for hormone-refractory prostate cancer, new therapeutic strategies are clearly needed," said Tomasz Beer, MD, an oncologist at the Oregon Health and Science University (OHSU) Cancer Institute in Portland, Oregon, and lead investigator of the study. "Docetaxel used alone has shown promise in treating prostate cancer, and our new data strongly indicate that the favorable results can be enhanced with the addition of high-dose vitamin D."
Tumor Reductions Noted
The study included 37 men with hormone-refractory prostate cancer, or disease that was progressive despite standard hormonal therapy, including antiandrogen withdrawal. In addition to PSA response, 8 of 15 men with measurable disease had significant reductions in tumor size.
Patients in the study received oral calcitriol, 0.5 µg/kg, on the first day of the treatment cycle, followed by an infusion of docetaxel, 36 mg/m², on the following day. Treatment was repeated weekly for 6 weeks of an 8-week cycle until there was evidence of disease progression or unacceptable toxicity, or until the patient requested to be withdrawn from the study.
The results of this phase II study are now the basis for a future phase III study to be conducted at OHSU and other institutions. That randomized study will evaluate the use of weekly docetaxel vs weekly docetaxel plus calcitriol in patients with hormone-refractory prostate cancer.