Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer.

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J Clin Oncol. 2003 Jan 1;21(1):123-8.

Comment in:
J Clin Oncol. 2003 May 15;21(10):2044-5; author reply 2045.

Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer.

Oregon Health & Science University and Portland VA Medical Center, Portland, OR 97239, USA. beert@ohsu.edu

PURPOSE: To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC).

PATIENTS AND METHODS: Thirty-seven patients were treated with oral calcitriol (0.5 micro g/kg) on day 1 followed by docetaxel (36 mg/m(2)) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 50% reduction in PSA level confirmed 4 weeks later.

RESULTS: Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a confirmed partial response. Median time to progression was 11.4 months (95% CI, 8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy.

CONCLUSION: The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well-tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC. Further study of this regimen is warranted.