RT Journal Article
SR Electronic
T1 Phase I/II Study of 19-<em>nor</em>-1α-25-Dihydroxyvitamin D<sub>2</sub> (Paricalcitol) in Advanced, Androgen-Insensitive Prostate Cancer
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 8680
OP 8685
DO 10.1158/1078-0432.CCR-05-1237
VO 11
IS 24
A1 Schwartz, Gary G.
A1 Hall, M. Craig
A1 Stindt, Diana
A1 Patton, Suzanne
A1 Lovato, James
A1 Torti, Frank M.
YR 2005
UL http://clincancerres.aacrjournals.org/content/11/24/8680.abstract
AB 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 toxicity 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 &lt; 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.