Peptide analogs in the therapy of prostate cancer

The use of peptide analogs in the therapy of prostate cancer is reviewed. T he preferred primary treatment of advanced androgen-dependent prostate canc er is presently based on the use of depot preparations of LH-RH agonists. T his treatment is likewise recommended in patients with rising PSA levels af ter surgery or radiotherapy. LH-RI-I agonists with or without antiandrogens can be also utilized prior to or following various local treatments in pat ients with clinically localized prostate cancer and at high risk for diseas e recurrence. LH-RH antagonists like Cetrorelix are in clinical trials. How ever, most patients with advanced prostatic carcinoma treated by any modali ty of androgen deprivation eventually relapse. Treatment of relapsed androg en-independent prostate cancer remains a major challenge, but new therapeut ic modalities are being developed based on antagonists of growth hormone-re leasing hormone (GH-RH) and bombesin, which inhibit growth factors or their receptors. Another approach consists of cytotoxic analogs of LH-RH, bombes in, and somatostatin containing doxorubicin or 2-pyrrolinodoxorubicin, whic h can be targeted to receptors for these peptides found in prostate cancers and their metastases. These cytotoxic analogs inhibit growth of experiment al androgen-dependent or -independent prostate cancers and reduce the incid ence of metastases. A rational therapy with peptide analogs could be select ed on the basis of receptors present in biopsy samples. The approaches base d on peptide analogs should result in a more effective treatment for prosta te cancer. Prostate 45:158-166, 2000. (C) 2000 Wiley-Liss, Inc.