High-dose calcitriol, zoledronate, and dexamethasone for the treatment of progressive prostate carcinoma.
Publication/Presentation Date
5-1-2004
Abstract
BACKGROUND: Preclinical and clinical data have suggested that high-dose calcitriol (1,25-dihydroxycholecalciferol) has activity against prostate carcinoma. Pulse-dosed calcitriol and dexamethasone may maximize tolerability and efficacy. The authors examined the toxicity of pulse-dosed calcitriol with zoledronate and with the addition of dexamethasone at the time of disease progression.
METHODS: Patients with progressive prostate carcinoma were eligible for the current study. In cohorts of 3-6 patients, calcitriol was administered for 3 consecutive days per week, starting at a dose of 4 microg per day. Doses were escalated to 30 microg per day. Intravenous zoledronate (4 mg) was administered monthly. Dexamethasone could be added to the regimen at disease progression. Toxicities, markers of bone turnover, plasma calcitriol levels, and clinical outcomes were recorded.
RESULTS: Thirty-one patients were treated in cohorts that were defined by the calcitriol dose administered (4, 6, 8, 10, 14, 20, 24, or 30 microg). Seven patients received dexamethasone. Three patients had their doses reduced due to calcium-related laboratory findings. Patients tolerated therapy well, even in the 30 microg cohort; therefore, a maximum tolerated dose was not defined. Peak plasma levels observed in the 24 microg and 30 microg cohorts ranged from 391 to 968 pg/mL. Minimal antitumor effects were observed.
CONCLUSIONS: Calcitriol was well tolerated at doses up to and including 30 microg 3 times per week in combination with intravenous zoledronate 4 mg monthly, with or without dexamethasone, in patients with progressive prostate carcinoma. Peak plasma levels in the 24 microg and 30 microg cohorts were greater than the levels associated with antitumor effects preclinically. Due to the cumbersome dosing schedule and the lack of significant activity observed, Phase II trials of this regimen are not planned.
Volume
100
Issue
9
First Page
1868
Last Page
1875
ISSN
0008-543X
Published In/Presented At
Morris, M. J., Smaletz, O., Solit, D., Kelly, W. K., Slovin, S., Flombaum, C., Curley, T., Delacruz, A., Schwartz, L., Fleisher, M., Zhu, A., Diani, M., Fallon, M., & Scher, H. I. (2004). High-dose calcitriol, zoledronate, and dexamethasone for the treatment of progressive prostate carcinoma. Cancer, 100(9), 1868–1875. https://doi.org/10.1002/cncr.20185
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
15112267
Department(s)
Administration and Leadership
Document Type
Article