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High Dose Calcitriol (1,25(OH)2 Vitamin D3) + Dexamethasone in Androgen Independent Prostate Cancer
FROM ASCO 2000 asco online genitourinary cancer
NEW YORK, NY, May 20, 2000 - In a study to be presented at the ASCO meeting, researchers at University of Pittsburgh Cancer Institute say that dexamethasone (Dex) boosts the anti-tumor effects of calcitriol (Rocaltrol) in hormone-independent prostate cancer (i.e. prostate cancer that has already been treated with hormone therapy and has come back).Calcitriol (trade name Rocaltrol) is a potent form of vitamin D (1,25(OH)2 Vitamin D3). Low vitamin D exposure, the researchers note, seems to increase the risk of prostate cancer. Evidence from lab experiments in a dish and in animals shows that calcitriol has anti-tumor effects on prostate cancer cell lines.
The Pittsburgh team is conducting a phase II trial of high dose calcitriol + dexamethasone in men with androgen insensitive prostate cancer.
They say that they have shown that "dexamethasone (Dex) enhances calcitriol antitumor effects and reduces calcitriol-induced hypercalcemia." Hypercalcemia is a problem with high doses of calcitriol. Calcium levels rise in the bloodstream and excess calcium may collect in body organs.
Thirty-two (32) patients with AIPC progressing despite anti-androgen withdrawal have been entered in the Pittsburgh Phase II trial.
Calcitriol is given orally in escalating dose levels of 8m g Monday, Tuesday, Wednesday (MTW) weekly x1 month; 10m g MTW, weekly x1 month and then 12m g MTW weekly. Dex is given 4 mg Sunday, MTW each week.
Patients are evaluable for response if they completed more than 1 month of 12 m g calcitriol MTW.
Of the 32 patients in the trial, 24 patients are evaluable, 4 too early to evaluate (TETE), 4 unevaluable. "Two patients have had mild and transient hypercalcemia. (12.1 mg/dL in each case). In neither case was cessation of treatment or dose reduction required."
Three patients withdrew from therapy due to moderate hypercortisolism (proximal myopathy), the authors report. One patient developed "an asymptomatic renal stone."
Among 24 patients evaluable, responses have been noted as follows:
Greater than fifty per cent drop in PSA (> 50% PSA): 5 (21%),
Drop in PSA velocity: 19 (79%).
The authors state: "These data indicate that high dose calcitriol + dexamethasone is safe; clear antitumor effects are evident. Studies continue to define the maximum dose of calcitriol which can be safely administered on this intermittent schedule and to evaluate the mechanisms of calcitriol effects."
Supported by CaPCURE, NCI CA 47904 and NCI CA 67267
Abstract 1327 High Dose Calcitriol (1,25(OH)2 Vitamin D3) + Dexamethasone in Androgen Independent Prostate Cancer (AIPC). Donald L. Trump, Stephanie Serafine, Adam Brufsky, Josephia Muindi, Ronald Bernardi, Douglas Potter, Candace Johnson, Univ of Pittsburgh Cancer Inst, Pittsburgh, PA.
Caution -- Calcitriol [Rocaltrol] and Hypercalcemia (Australian Adverse Drug Reactions Bulletin)
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