REVERSAL OF CLINICAL RESISTANCE TO LHRH ANALOG IN METASTATIC PROSTATE-CANCER BY THE PINEAL HORMONE MELATONIN - EFFICACY OF LHRH ANALOG PLUSMELATONIN IN PATIENTS PROGRESSING ON LHRH ANALOG ALONE

Objective: Experimental and preliminary clinical studies have suggeste d that the pineal hormone melatonin (MLT) may stimulate hormone recept or expression on both normal and cancer cells. Moreover, MLT has appea red to inhibit the growth of some cancer cell lines, including prostat e cancer, either by exerting a direct cytostatic action, or by decreas ing the endogenous production of some tumor growth factors, such as pr olactin (PRL) and insulin-like growth factor-1 (IGF-I). On this basis, a study was carried out to evaluate the clinical efficacy of a neuroe ndocrine combination consisting of the LHRH analogue triptorelin plus MLT in metastatic prostate cancer progressing on triptorelin alone. Ma terial and Methods: The study including 14 consecutive metastatic pros tate cancer patients with poor clinical conditions (median age: 70.5 y ears; median PS: 50%), refractory or resistant to a previous therapy w ith the LHRH analogue triptorelin alone, Triptorelin was injected i.m. at 3.75 mg every 28 days, and MLT was given orally at 20 mg/day in th e evening every day until progression, starting 7 days prior to tripto relin. Results and Conclusions: A decrease in PSA serum levels greater than 50% was obtained in 8/14 (57%) patients. Moreover, PSA mean conc entrations significantly decreased on therapy of triptorelin plus MLT. In addition, a normalization of platelet number was obtained in 3/5 p atients with persistent thrombocytopenia prior to study, Mean serum le vels of both PRL and IGF-I significantly decreased on therapy. Finally , a survival longer than I year was achieved in 9/14 (64%) patients. T his preliminary study would suggest that the concomitant administratio n of the pineal hormone MLT may overcome the clinical resistance to LH RH analogues and improve the clinical conditions in metastatic prostat ic cancer patients.