Phase I/II study of 19-nor-1alpha-25-dihydroxyvitamin D2 (paricalcitol) in advanced, androgen-insensitive prostate cancer.
OBJECTIVE
We assessed the safety and efficacy of the vitamin D analogue, 19-nor-1alpha-25-dihydroxyvitamin D2 (paricalcitol), in patients with androgen-independent prostate cancer.


METHODS
Patients received paricalcitol i.v. three times per week on an escalating dose of 5 to 25 microg (3-15 microg/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 microg). 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).


CONCLUSIONS
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.
Schwartz
Gary G
GG
Department of Cancer Biology, Wake Forest University, Winston-Salem, NC 27157, and Nortwest Georgia Oncology Centers, Douglasville, USA.
Hall
M Craig
MC
Stindt
Diana
D
Patton
Suzanne
S
Lovato
James
J
Torti
Frank M
FM
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000728:Androgens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D004872:Ergocalciferols / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D000728:Androgens; D000970:Antineoplastic Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; C084656:paricalcitol; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen; D002118:Calcium