Phase I/II study of 19-nor-1α-25-dihydroxyvitamin D2 (paricalcitol) in advanced, androgen-insensitive prostate cancer

Gary G. Schwartz, M. Craig Hall, Diana Stindt, Suzanne Patton, James Lovato, Frank M. Torti

Research output: Contribution to journalArticle

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Abstract

Purpose: We assessed the safety and efficacy of the vitamin D analogue, 19-nor-1α-25-dihydroxyvitamin D2 (paricalcitol), in patients with androgen-independent prostate cancer. Experimental Design: Patients received paricalcitol i.v. three times per week on an escalating dose of 5 to 25 μg (3-15 μg/m2). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were characterization of toxtcity in this population, changes in serum parathyroid hormone (PTH), and survival. Results: A total of 18 patients were enrolled. No patient showed a sustained 50% drop in serum PSA, despite several large declines in PSA (e.g., 1,300 ng/mL). Paricalcitol was well tolerated. One instance of significant hypercalcemia, a serum calcium of 14.3 mg/dL, was observed at the highest dose (25 μg). At entry into the study, seven (41%) of the patients had elevated serum levels of PTH, which were significantly reduced by paricalcitol. Higher levels of serum PTH at study entry were significantly and negatively associated with survival (P < 0.01). Conclusion: No objective responses were seen in the primary end point. However, elevated serum levels of PTH, a common feature of advanced prostate cancer, were reduced by paricalcitol. Because elevated PTH is associated with increased cardiovascular and skeletal morbidity, including an increased risk for pathologic fracture, further evaluation of paricalcitol in the reduction of skeletal morbidity in advanced prostate cancer is warranted.

Original languageEnglish (US)
Pages (from-to)8680-8685
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number24
DOIs
StatePublished - Dec 15 2005

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Androgens
Prostatic Neoplasms
Parathyroid Hormone
Prostate-Specific Antigen
Serum
Morbidity
Spontaneous Fractures
Survival
Hypercalcemia
Vitamin D
1,25-dihydroxyergocalciferol
paricalcitol
Research Design
Calcium
Safety
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase I/II study of 19-nor-1α-25-dihydroxyvitamin D2 (paricalcitol) in advanced, androgen-insensitive prostate cancer. / Schwartz, Gary G.; Hall, M. Craig; Stindt, Diana; Patton, Suzanne; Lovato, James; Torti, Frank M.

In: Clinical Cancer Research, Vol. 11, No. 24, 15.12.2005, p. 8680-8685.

Research output: Contribution to journalArticle

Schwartz, Gary G. ; Hall, M. Craig ; Stindt, Diana ; Patton, Suzanne ; Lovato, James ; Torti, Frank M. / Phase I/II study of 19-nor-1α-25-dihydroxyvitamin D2 (paricalcitol) in advanced, androgen-insensitive prostate cancer. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 24. pp. 8680-8685.
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abstract = "Purpose: We assessed the safety and efficacy of the vitamin D analogue, 19-nor-1α-25-dihydroxyvitamin D2 (paricalcitol), in patients with androgen-independent prostate cancer. Experimental Design: Patients received paricalcitol i.v. three times per week on an escalating dose of 5 to 25 μg (3-15 μg/m2). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were characterization of toxtcity in this population, changes in serum parathyroid hormone (PTH), and survival. Results: A total of 18 patients were enrolled. No patient showed a sustained 50{\%} drop in serum PSA, despite several large declines in PSA (e.g., 1,300 ng/mL). Paricalcitol was well tolerated. One instance of significant hypercalcemia, a serum calcium of 14.3 mg/dL, was observed at the highest dose (25 μg). At entry into the study, seven (41{\%}) of the patients had elevated serum levels of PTH, which were significantly reduced by paricalcitol. Higher levels of serum PTH at study entry were significantly and negatively associated with survival (P < 0.01). Conclusion: No objective responses were seen in the primary end point. However, elevated serum levels of PTH, a common feature of advanced prostate cancer, were reduced by paricalcitol. Because elevated PTH is associated with increased cardiovascular and skeletal morbidity, including an increased risk for pathologic fracture, further evaluation of paricalcitol in the reduction of skeletal morbidity in advanced prostate cancer is warranted.",
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