title: A phase II study of tamoxifen in hormone-resistant metastatic prostate cancer: possible relation with prolactin secretion.
abstract: Recent experimental observations, showing the potential role of prolactin (PRL) as a tumor growth factor for prostate cancer and the unfavourable prognostic significance of enhanced chromogranin-A-secreting neuroendocrine cell proliferation, could contribute to a better understanding of the mechanisms responsible for the occurrence of hormone-resistance in the prostate cancer. Moreover, it has been shown that tamoxifen, which consistently exerts estrogenic activity in males, may inhibit prostate cancer cell proliferation in experimental studies. At present, there are no clinical data in humans. This preliminary phase II study was planned in an attempt to evaluate the therapeutic efficacy of tamoxifen in hormone-refractory metastatic prostate cancer. The study included 14 consecutive metastatic prostate cancer patients, who had progressed under the classical endocrine therapy with LHRH-analogs and/or anti-androgens. Patients received the same treatment plus tamoxifen at 20 mg/day orally. A decline greater than 50% in prostate-specific antigen (PSA) levels occurred in 4/14 (29%) patients within the first 2 months of therapy, with a median duration of 5 months. Mean pre-treatment levels of PRL were significantly higher in responder patients than in those who progressed. Moreover, abnormally high pre-treatment levels of PRL were found in 5/14 (36%) patients. The percent of clinical responses observed in patients with pre-treatment hyperprolactinemia was significantly higher than that found in patients with normal pre-treatment PRL concentrations. Finally, a significant decline in mean PRL levels upon tamoxifen therapy occurred only in the responder patients. This preliminary study seems to justify further clinical research to confirm the potential efficacy of tamoxifen in the treatment of hormone-refractory prostate cancer and to identify possible parameters, which may predict the response to treatment.
authors.affiliation: Division of Radiation Oncology, San Gerardo Hospital, Monza, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lissoni
authors.forename: P
authors.initials: P
authors.lastname: Vigano
authors.forename: M
authors.initials: M
authors.lastname: Vaghi
authors.forename: L
authors.initials: L
authors.lastname: Frontini
authors.forename: C
authors.initials: C
authors.lastname: Giuberti
authors.forename: V
authors.initials: V
authors.lastname: Manganini
authors.forename: M
authors.initials: M
authors.lastname: Casu
authors.forename: F
authors.initials: F
authors.lastname: Brivio
authors.forename: R
authors.initials: R
authors.lastname: Niespolo
authors.forename: G
authors.initials: G
authors.lastname: Strada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin