Effect of 13-cis-retinoic acid on serum prostate-specific antigen levels in patients with recurrent prostate cancer after radical prostatectomy

The objective of this study was to determine whether there is any beneficia l effect of oral 13-cis-retinoic acid (isotretinoin) on prostate cancer, us ing serum prostate-specific antigen (PSA) levels as a surrogate end point i n patients with a rising serum PSA after radical prostatectomy, In the firs t phase, the effect of the drug on the serum PSA level was tested in 14 con trol patients with normal prostates. Our goal was to exclude any effect of isotretinoin on PSA secretion and metabolism and thus to validate any obser ved effect on PSA as indicative of anticancer activity. In the second phase , patients with rising PSA levels after radical prostatectomy and no eviden ce of metastatic disease were treated with oral isotretinoin at a daily dos e of 1.0 mg/kg, Serum PSA levels were checked monthly for the first 4 month s after initiation of treatment and every 3 months thereafter. No significa nt changes in serum PSA levels after 3 months of isotretinoin treatment wer e recorded in the control group (P = 1.000), Three of 11 postprostatectomy patients (27%) had a PSA reduction of 28%, 15%, and 6.6% after initiation o f treatment that lasted for a period of 2 3 months. In two of these three p atients, the PSA levels subsequently rose exponentially. Another patient di splayed a stabilization of the serum PSA curve for 3 months after an initia l sharp rise. No grade 3 or 4 toxicity was recorded in this group of patien ts. Isotretinoin had a modest, transient effect on the serum PSA level in 4 of 11 (36%) patients with a rising serum PSA after radical prostatectomy, We conclude that this drug is unlikely to be of major therapeutic benefit i n prostate cancer patients when used as a single agent. However, its modest effect argues for the exploration of other, more potent retinoids for pros tate cancer therapy.