High-dose calcitriol, zoledronate, and dexamethasone for the treatment of progressive prostate carcinoma Journal Article


Authors: 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.
Article Title: High-dose calcitriol, zoledronate, and dexamethasone for the treatment of progressive prostate carcinoma
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 μg per day. Doses were escalated to 30 μg 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 μg). Seven patients received dexamethasone. Three patients had their doses reduced due to calcium-related laboratory findings. Patients tolerated therapy well, even in the 30 μg cohort; therefore, a maximum tolerated dose was not defined. Peak plasma levels observed in the 24 μg and 30 μg 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 μg 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 μg and 30 μg 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. © 2004 American Cancer Society.
Keywords: adult; cancer chemotherapy; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; survival analysis; clinical trial; constipation; drug tolerability; fatigue; cancer growth; hypophosphatemia; side effect; cancer patient; drug megadose; follow-up studies; neoplasm staging; prospective studies; controlled clinical trial; lung toxicity; nephrotoxicity; cohort studies; anemia; blood toxicity; neuropathy; myalgia; drug administration schedule; cohort analysis; bisphosphonates; calcium; creatinine; dexamethasone; bone pain; calcium blood level; creatinine blood level; hypercalcemia; calcitriol; antineoplastic activity; dose-response relationship, drug; risk assessment; arthralgia; hyperglycemia; pneumonia; prostatic neoplasms; gastrointestinal toxicity; prothrombin time; drug therapy, combination; disease progression; laboratory test; thrombosis; vitamin d; carcinoma; medical documentation; drug blood level; maximum tolerated dose; toxicity; drug dose regimen; urogenital tract disease; diphosphonates; metabolic disorder; zoledronic acid; imidazoles; dysuria; prostate carcinoma; hypocalcemia; hydronephrosis; bone turnover; hypercalciuria; nephrolithiasis; pulse therapy, drug; humans; human; male; priority journal; article; steroid hormones; rocatrol
Journal Title: Cancer
Volume: 100
Issue: 9
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2004-05-01
Start Page: 1868
End Page: 1875
Language: English
DOI: 10.1002/cncr.20185
PROVIDER: scopus
PUBMED: 15112267
DOI/URL:
Notes: Cancer -- Cited By (since 1996):19 -- Export Date: 16 June 2014 -- CODEN: CANCA -- Source: Scopus
Altmetric Score
MSK Authors
  1. Susan Slovin
    186 Slovin
  2. Michael Morris
    280 Morris
  3. William K Kelly
    110 Kelly
  4. David Solit
    440 Solit
  5. Andrew X Zhu
    6 Zhu
  6. Lawrence H Schwartz
    281 Schwartz
  7. Martin Fleisher
    242 Fleisher
  8. Howard Scher
    835 Scher
  9. Meghan Diani
    5 Diani
  10. Mary E Warren
    7 Warren