Decreased toxicity and increased efficacy of cancer chemotherapy using thepineal hormone melatonin in metastatic solid tumour patients with poor clinical status

Melatonin (MLT) has been proven to counteract chemotherapy toxicity, by act ing as an anti-oxidant agent, and to promote apoptosis of cancer cells, so enhancing chemotherapy cytotoxicity. The aim of this study was to evaluate the effects of concomitant MLT administration on toxicity and efficacy of s everal chemotherapeutic combinations in advanced cancer patients with poor clinical status. The study included 250 metastatic solid tumour patients (l ung cancer, 104; breast cancer, 77; gastrointestinal tract neoplasms, 42; h ead and neck cancers, 27), who were randomised to receive MLT (20 mg/day or ally every day) plus chemotherapy, or chemotherapy alone. Chemotherapy cons isted of cisplatin (CDDP) plus etoposide or gemcitabine alone for lung canc er, doxorubicin alone, mitoxantrone alone or paclitaxel alone for breast ca ncer, 5-FU plus folinic acid for gastro-intestinal tumours and 5-FU plus CD DP for head and neck cancers. The 1-year survival rate and the objective tu mour regression rate were significantly higher in patients concomitantly tr eated with MLT than in those who received chemotherapy (CT) alone (tumour r esponse rate: 42/124 CT + MLT versus 19/126 CT only, P<0.001; 1-year surviv al: 63/124 CT + MLT versus 29/126 CT only, P<0.001). Moreover, the concomit ant administration of MLT significantly reduced the frequency of thrombocyt openia, neurotoxicity, cardiotoxicity, stomatitis and asthenia. This study indicates that the pineal hormone MLT may enhance the efficacy of chemother apy and reduce its toxicity, at least in advanced cancer patients of poor c linical status. (C) 1999 Elsevier Science Ltd. All rights reserved.