Phase II study of nitric oxide donor for men with increasing prostate-specific antigen level after surgery or radiotherapy for prostate cancer.

OBJECTIVES

To evaluate the effect of low-dose glyceryl trinitrate (GTN) on men with biochemical recurrence of prostate cancer after primary therapy. Preclinical, proof-of-principle studies have demonstrated that nitric oxide signaling plays a significant role in the hypoxia-induced progression of prostate cancer.

METHODS

A prospective, open-label clinical trial of men with an increasing prostate-specific antigen (PSA) level after surgery or radiotherapy was conducted. Men with PSA recurrence were enrolled in a 24-month trial investigating the effect of a low-dose, slow-release transdermal GTN patch. The PSA doubling time (PSADT) was compared before and after treatment initiation, as well as with a matched control group that received no immediate treatment for their PSA recurrence.

RESULTS

A total of 29 patients were enrolled in the study. Of the 29 patients, 62% completed the 24-month protocol, with 10% experiencing clinical disease progression. The calculated PSADT of the treatment group before initiating GTN was 13.3 months, not significantly different from that of the matched control group at 12.8 months. In an intention-to-treat analysis, the end-of-study PSADT for the treatment group was significantly different at 31.8 months (P < .001).

CONCLUSIONS

We report the first clinical trial of a GTN patch in patients with prostate cancer. The prolongation of the PSADT and the safety of the drug, coupled with the corresponding preclinical in vitro and in vivo data documenting the ability of nitric oxide to attenuate hypoxia-induced progression of prostate cancer, warrant further testing in a placebo-controlled study.