Weekly high-dose calcitriol and docetaxel in advanced prostate cancer

Tomasz (Tom) Beer, Kristine M. Hough, Mark Garzotto, Bruce A. Lowe, W. David Henner

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Novel treatment regimens for androgen-independent prostate cancer (AIPC) are needed because currently available approaches have not been shown to improve survival. Docetaxel provides a good foundation for new therapeutic combinations because of its promising single-agent activity against prostate cancer and its favorable tolerability profile, particularly when administered weekly. In both tissue culture and animal models of prostate cancer, calcitriol (the biologically active form of vitamin D) enhanced the activity of docetaxel, paclitaxel, and platinum compounds. These effects were particularly notable at supraphysiologic calcitriol concentrations. Weekly calcitriol dosing is associated with minimal toxicity and permits substantial dose escalation over the daily schedule. A weekly calcitriol dose of 0.5 μg/kg produces plasma calcitriol levels 25-fold higher than the physiologic range. In a preclinical study at the Oregon Health Sciences University, calcitriol 5 μmol/L plus docetaxel 0.15 nmol/L was at least additive in inhibiting PC-3 colony formation. A phase II study is evaluating weekly administration of 0.5 μ/kg calcitriol orally on day 1 followed by 36 mg/m 2 docetaxel intravenously on day 2 in patients with AIPC (repeated for 6 consecutive weeks of each 8-week cycle). At the time of a preliminary analysis, 11 patients had been enrolled and were actively being treated. All 5 patients who had completed 8 weeks of calcitriol/docetaxel treatment achieved prostate-specific antigen (PSA) reductions of ≥50%. Two of these patients had confirmatory assessments, both meeting the formal PSA response criteria. Treatment has been well tolerated, with 1 patient experiencing a self-limited grade 3 toxicity and no patients experiencing grade 4 or 5 toxicities.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalSeminars in Oncology
Volume28
Issue number4 SUPPL. 15
StatePublished - 2001

Fingerprint

docetaxel
Calcitriol
Prostatic Neoplasms
Prostate-Specific Antigen
Androgens
Platinum Compounds
Therapeutics
Paclitaxel
Vitamin D

ASJC Scopus subject areas

  • Oncology

Cite this

Beer, T. T., Hough, K. M., Garzotto, M., Lowe, B. A., & Henner, W. D. (2001). Weekly high-dose calcitriol and docetaxel in advanced prostate cancer. Seminars in Oncology, 28(4 SUPPL. 15), 49-55.

Weekly high-dose calcitriol and docetaxel in advanced prostate cancer. / Beer, Tomasz (Tom); Hough, Kristine M.; Garzotto, Mark; Lowe, Bruce A.; Henner, W. David.

In: Seminars in Oncology, Vol. 28, No. 4 SUPPL. 15, 2001, p. 49-55.

Research output: Contribution to journalArticle

Beer, TT, Hough, KM, Garzotto, M, Lowe, BA & Henner, WD 2001, 'Weekly high-dose calcitriol and docetaxel in advanced prostate cancer', Seminars in Oncology, vol. 28, no. 4 SUPPL. 15, pp. 49-55.
Beer, Tomasz (Tom) ; Hough, Kristine M. ; Garzotto, Mark ; Lowe, Bruce A. ; Henner, W. David. / Weekly high-dose calcitriol and docetaxel in advanced prostate cancer. In: Seminars in Oncology. 2001 ; Vol. 28, No. 4 SUPPL. 15. pp. 49-55.
@article{6df14c50a23e4e87bc28f71881208472,
title = "Weekly high-dose calcitriol and docetaxel in advanced prostate cancer",
abstract = "Novel treatment regimens for androgen-independent prostate cancer (AIPC) are needed because currently available approaches have not been shown to improve survival. Docetaxel provides a good foundation for new therapeutic combinations because of its promising single-agent activity against prostate cancer and its favorable tolerability profile, particularly when administered weekly. In both tissue culture and animal models of prostate cancer, calcitriol (the biologically active form of vitamin D) enhanced the activity of docetaxel, paclitaxel, and platinum compounds. These effects were particularly notable at supraphysiologic calcitriol concentrations. Weekly calcitriol dosing is associated with minimal toxicity and permits substantial dose escalation over the daily schedule. A weekly calcitriol dose of 0.5 μg/kg produces plasma calcitriol levels 25-fold higher than the physiologic range. In a preclinical study at the Oregon Health Sciences University, calcitriol 5 μmol/L plus docetaxel 0.15 nmol/L was at least additive in inhibiting PC-3 colony formation. A phase II study is evaluating weekly administration of 0.5 μ/kg calcitriol orally on day 1 followed by 36 mg/m 2 docetaxel intravenously on day 2 in patients with AIPC (repeated for 6 consecutive weeks of each 8-week cycle). At the time of a preliminary analysis, 11 patients had been enrolled and were actively being treated. All 5 patients who had completed 8 weeks of calcitriol/docetaxel treatment achieved prostate-specific antigen (PSA) reductions of ≥50{\%}. Two of these patients had confirmatory assessments, both meeting the formal PSA response criteria. Treatment has been well tolerated, with 1 patient experiencing a self-limited grade 3 toxicity and no patients experiencing grade 4 or 5 toxicities.",
author = "Beer, {Tomasz (Tom)} and Hough, {Kristine M.} and Mark Garzotto and Lowe, {Bruce A.} and Henner, {W. David}",
year = "2001",
language = "English (US)",
volume = "28",
pages = "49--55",
journal = "Seminars in Oncology",
issn = "0093-7754",
publisher = "W.B. Saunders Ltd",
number = "4 SUPPL. 15",

}

TY - JOUR

T1 - Weekly high-dose calcitriol and docetaxel in advanced prostate cancer

AU - Beer, Tomasz (Tom)

AU - Hough, Kristine M.

AU - Garzotto, Mark

AU - Lowe, Bruce A.

AU - Henner, W. David

PY - 2001

Y1 - 2001

N2 - Novel treatment regimens for androgen-independent prostate cancer (AIPC) are needed because currently available approaches have not been shown to improve survival. Docetaxel provides a good foundation for new therapeutic combinations because of its promising single-agent activity against prostate cancer and its favorable tolerability profile, particularly when administered weekly. In both tissue culture and animal models of prostate cancer, calcitriol (the biologically active form of vitamin D) enhanced the activity of docetaxel, paclitaxel, and platinum compounds. These effects were particularly notable at supraphysiologic calcitriol concentrations. Weekly calcitriol dosing is associated with minimal toxicity and permits substantial dose escalation over the daily schedule. A weekly calcitriol dose of 0.5 μg/kg produces plasma calcitriol levels 25-fold higher than the physiologic range. In a preclinical study at the Oregon Health Sciences University, calcitriol 5 μmol/L plus docetaxel 0.15 nmol/L was at least additive in inhibiting PC-3 colony formation. A phase II study is evaluating weekly administration of 0.5 μ/kg calcitriol orally on day 1 followed by 36 mg/m 2 docetaxel intravenously on day 2 in patients with AIPC (repeated for 6 consecutive weeks of each 8-week cycle). At the time of a preliminary analysis, 11 patients had been enrolled and were actively being treated. All 5 patients who had completed 8 weeks of calcitriol/docetaxel treatment achieved prostate-specific antigen (PSA) reductions of ≥50%. Two of these patients had confirmatory assessments, both meeting the formal PSA response criteria. Treatment has been well tolerated, with 1 patient experiencing a self-limited grade 3 toxicity and no patients experiencing grade 4 or 5 toxicities.

AB - Novel treatment regimens for androgen-independent prostate cancer (AIPC) are needed because currently available approaches have not been shown to improve survival. Docetaxel provides a good foundation for new therapeutic combinations because of its promising single-agent activity against prostate cancer and its favorable tolerability profile, particularly when administered weekly. In both tissue culture and animal models of prostate cancer, calcitriol (the biologically active form of vitamin D) enhanced the activity of docetaxel, paclitaxel, and platinum compounds. These effects were particularly notable at supraphysiologic calcitriol concentrations. Weekly calcitriol dosing is associated with minimal toxicity and permits substantial dose escalation over the daily schedule. A weekly calcitriol dose of 0.5 μg/kg produces plasma calcitriol levels 25-fold higher than the physiologic range. In a preclinical study at the Oregon Health Sciences University, calcitriol 5 μmol/L plus docetaxel 0.15 nmol/L was at least additive in inhibiting PC-3 colony formation. A phase II study is evaluating weekly administration of 0.5 μ/kg calcitriol orally on day 1 followed by 36 mg/m 2 docetaxel intravenously on day 2 in patients with AIPC (repeated for 6 consecutive weeks of each 8-week cycle). At the time of a preliminary analysis, 11 patients had been enrolled and were actively being treated. All 5 patients who had completed 8 weeks of calcitriol/docetaxel treatment achieved prostate-specific antigen (PSA) reductions of ≥50%. Two of these patients had confirmatory assessments, both meeting the formal PSA response criteria. Treatment has been well tolerated, with 1 patient experiencing a self-limited grade 3 toxicity and no patients experiencing grade 4 or 5 toxicities.

UR - http://www.scopus.com/inward/record.url?scp=0034788877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034788877&partnerID=8YFLogxK

M3 - Article

C2 - 11685729

AN - SCOPUS:0034788877

VL - 28

SP - 49

EP - 55

JO - Seminars in Oncology

JF - Seminars in Oncology

SN - 0093-7754

IS - 4 SUPPL. 15

ER -