MODULATION OF CANCER ENDOCRINE THERAPY BY MELATONIN - A PHASE-II STUDY OF TAMOXIFEN PLUS MELATONIN IN METASTATIC BREAST-CANCER PATIENTS PROGRESSING UNDER TAMOXIFEN ALONE

Recent observations have shown that the pineal hormone melatonin (MLT) may modulate oestrogen receptor (ER) expression and inhibit breast ca ncer cell growth. On this basis, we have evaluated the biological and clinical effects of a concomitant MLT therapy in women with metastatic breast cancer who had progressed in response to tamoxifen (TMX) alone . The study included 14 patients with metastasis who did not respond ( n = 3) to therapy with TMX alone or progressed after initial stable di sease (SD) (n = 11). MLT was given orally at 20 mg day(-1) in the even ing, every day starting 7 days before TMX, which was given orally at 2 0 mg day(-1) at noon. A partial response was achieved in 4/14 (28.5%) patients (median duration 8 months). The treatment was well tolerated in all cases, and no MLT-induced enhancement of TMX toxicity was seen; on the contrary, most patients experienced a relief of anxiety. Mean serum levels of insulin-like growth factor 1 (IGF-1), which is a growt h factor for breast cancer, significantly decreased on therapy, and th is decline was significantly higher in responders than in patients wit h SD or progression. This pilot phase II study would suggest that the concomitant administration of the pineal hormore MLT may induce object ive tumour regressions in metastatic breast cancer patients refractory to TMX alone.