A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first‐line treatment of advanced non‐small cell lung cancer patients in a poor clinical state

Abstract

Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage. In addition, melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production. On this basis, we have performed a randomized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients (NSCLC) with poor clinical status. The study included 70 consecutive advanced NSCLC patients who were randomized to receive chemotherapy alone with cisplatin (20 mg/m2/day i.v. for 3 days) and etoposide (100 mg/m2/day i.v. for 3 days) or chemotherapy plus melatonin (20 mg/day orally in the evening). Cycles were repeated at 21-day intervals. Clinical response and toxicity were evaluated according to World Health Organization criteria. A complete response (CR) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone. Partial response (PR) occurred in 10/34 and in 6/36 patients treated with or without melatonin, respectively. Thus, the tumor response rate was higher in patients receiving melatonin (11/34 vs. 6/35), without, however, statistically significant differences. The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone (15/34 vs. 7/36, P < 0.05). Finally, chemotherapy was well tolerated in patients receiving melatonin, and in particular the frequency of myelosuppression, neuropathy, and cachexia was significantly lower in the melatonin group. This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy, mainly in terms of survival time, and reduce chemotherapeutic toxicity in advanced NSCLC, at least in patients in poor clinical condition.

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

“…(19,20,21,22,23,11,24,25,26,27,28,29,30,31,32,33) Three independent randomized trials, including this trial, have been run. (34,35) It is noteworthy that all of the trials from Lissoni and colleagues have had positive outcomes and, as of yet, there have been no confirmatory publications from outside of his group.…”

Circadian function in patients with advanced non-small-cell lung cancer

“…Lissoni's group reports that melatonin reduces the toxicity of various chemotherapeutic agents, including Cisplatin, Etoposide, Anthracyclines, and 5-Flourouracil. They found a statistically significant reduction in treatment-related adverse events, such as myelosuppression, neurotoxicity, nephrotoxicity, cardiotoxicity, and asthenia (Lissoni et al, 1992(Lissoni et al, , 1994(Lissoni et al, , 1997(Lissoni et al, , 1999.…”

Perspectives of Melatonin Use in Clinical Oncology

“…В исследование включено было 70 пациентов. 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].…”