A Phase II Study of Tamoxifen in Hormone-resistant Metastatic Prostate Cancer: Possible Relation with Prolactin Secretion

• Published in: Anticancer research Vol. 25; no. 5; pp. 3597 - 3599
• Main Authors: LISSONI, P, VIGANO, P, VAGHI, M, FRONTINI, L, GIUBERTI, C, MANGANINI, V, CASU, M, BRIVIO, F, NIESPOLO, R, STRADA, G
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-09-2005
• Subjects: Aged; Aged, 80 and over; Androgen Antagonists - therapeutic use; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Drug Resistance, Neoplasm; Gonadotropin-Releasing Hormone - analogs & derivatives; Humans; Male; Medical sciences; Middle Aged; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - secretion; Nephrology. Urinary tract diseases; Prolactin - secretion; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - secretion; Tamoxifen - therapeutic use; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Antineoplastic agent; Urinary system disease; Prostate disease; Secretion; Antiestrogen; Antihormone; Malignant tumor; Metastasis; Tamoxifene; Resistance; Cancerology; Treatment; Adenohypophyseal hormone; Prolactin; Phase II trial; Advanced stage; Male genital diseases; Non steroid compound; Prostate cancer; Hormone resistance; tamoxifen
• ISSN: 0250-7005; 1791-7530

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.