Five years survival in metastatic non‐small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial

Abstract

Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms.

The contribution of circadian rhythms to cancer formation and mortality

“…In addition, the average progression-free time was approximately 4 months for the group receiving chemotherapy alone and was 9 months for the melatonin group, and the majority of chemotherapyrelated toxicities had less than half the frequency in the melatonin and chemotherapy versus the chemotherapy alone group (Lissoni et al, 1999). Similar levels of increased chemotherapy tolerance, higher survival, and increased response were also found in a five-year study of 100 patients with non-small lung cancer (Lissoni et al, 2003). Other studies have reported consistent results of increased survival, tolerance, progressionfree time, as well as reductions in anxiety and pain (Vijayalaxmi et al, 2002).…”

Perspectives of Melatonin Use in Clinical Oncology

“…В группе с мелатонином было большее число объектив-ных ответов (11/34 по сравнению с 6/35), однако различия не были статистически значимы и увеличение медианы общей выживаемости с 19% до 44% (р<0.05) [46]. В по-следующем анализе данных было показано, что 6% боль-ных с НМРЛ, получавших химиотерапию с МЛТ, достигли 5-летней выживаемости, в то время как пациенты из груп-пы стандартной химиотерапии не пережили 2 года [47]. Еще одно исследование включало 250 пациентов с мета-статическими солидными опухолями -РМЖ, КРР, ОГШ, РЖ -которые получали стандартную химиотерапию с или без МЛТ 20 мг внутрь ежедневно.…”

Should Patients Undergoing Chemotherapy and Radiotherapy Be Prescribed Antioxidants?

“…In 2003, Paolo Lissoni, MD, chief of oncology at a large public hospital in northern Italy, and colleagues, showed that melatonin can "modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity." 54 It was only the latest in a long line of positive clinical trials on this topic.…”

“…54 In 2003, Lissoni and colleagues looked at 5-year survival rates from metastatic NSCLC. One hundred patients received the standard drugs cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/d orally in the evening).…”