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).

PATIENTS AND 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.