Dose-Dependency of Antitumor Effects of the Pineal Hormone Melatonin in Untreatable Metastatic Solid Tumor Patients

Abstract

Despite it is known since more than 50 years that the pineal hormone melatonin (MLT) may play an anticancer activity, as confirmed by several experimental and clinical studies, the clinical use of MLT in the treatment of cancer is still at the beginning. Most clinical studies have been performed with MLT dose of 20 mg/once daily in the dark period. Preliminary clinical studies with MLT in untreatable advanced cancer patients have demonstrated an inhibitory effect on tumor progression, with a prolonged 1-year survival. However, at present it is still unknown whether the antitumor action of MLT may be a dose-dependent event in human neoplasms. This preliminary study was performed to evaluate the doseefficacy ratio of MLT in the treatment of human neoplasms. The study was performed in 14 consecutive metastatic solid tumor patients, for whom no other standard antitumor therapy was available. MLT was administered at a dose of 20 mg/day orally in the evening. In the case of progressive disease, MLT dose was progressively enhanced until 100 mg/day. MLT therapy at a dose of 20 mg/day induced a disease control in 7/145 patients, consisting of partial response (PR) in one patient and a stable disease (SD) in other 6 patients. After progression, dose increase of MLT until 100 mg induced again a SD in 6/14 (43%) and 1–year survival was achieved in 8/14 (56%). The results of this preliminary study would demonstrate that the antitumor activity of MLT may increase by increasing MLT dose, and then it seems to be a dose-dependent phenomenon.