The addition of high-dose calcitriol (the active form
of vitamin D) to weekly treatment with 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
"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until the patient requested to be withdrawn from the study.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.