A phase II study of high-dose calcitriol combined with mitoxantrone and prednisone for androgen-independent prostate cancer.
OBJECTIVE
To evaluate the preliminary efficacy, safety, and impact on quality of life (QoL) of high-dose calcitriol (DN-101) combined with mitoxantrone and glucocorticoids in androgen-independent prostate cancer (AIPC).


METHODS
Nineteen patients with metastatic AIPC and no previous chemotherapy received DN-101 180 microg orally on day 1 and mitoxantrone 12 mg/m(2) intravenously on day 2 every 21 days with continuous daily prednisone 10 mg orally for a maximum of 12 cycles. A confirmed decline in prostate-specific antigen (PSA) levels by half was the primary endpoint. QoL was evaluated using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, and pain and analgesic use were evaluated.


RESULTS
Five of 19 patients (26%; 95% confidence interval, CI, 9-51) achieved a >/=50% decline in PSA level. The median (95% CI) time to PSA progression was 16 (6-26) weeks. The overall median (95% CI) survival was 16 (6-26) months; 47 (21-73)% of patients achieved an analgesic response. Toxicity was similar to that expected with mitoxantrone and prednisone alone. The QoL analysis suggested a decrease in physical functioning and increase in fatigue, insomnia, and diarrhoea.


CONCLUSIONS
DN-101 given every 3 weeks does not add significant activity to mitoxantrone and prednisone in AIPC, as measured by the PSA decline. The high rate of analgesic response is encouraging. The addition of DN-101 does not appear to increase the toxicity of mitoxantrone.
Chan
Joseph S
JS
Oregon Health & Science University, Portland, OR 97239, USA.
Beer
Tomasz M
TM
Quinn
David I
DI
Pinski
Jacek K
JK
Garzotto
Mark
M
Sokoloff
Mitchell
M
Dehaze
Daniel R
DR
Ryan
Christopher W
CW
D000230:Adenocarcinoma / Q000188:drug therapy*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002117:Calcitriol / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D016896:Treatment Outcome
D000728:Androgens; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; D002117:Calcitriol; D011241:Prednisone