A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma

Abstract

Summary Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 (IL-2) is not co-administration of another cytokine, but the association with immunomodulating neurohormones, in an attempt to reproduce the physiological links between psychoendocrine and immune systems, which play a fundamental role in the regulation of the immune responses. In particular, the association with the pineal neurohormone melatonin (MLT) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone. To confirm these preliminary results, a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma. The study included 80 consecutive patients, who were randomised to be treated with IL-2 alone subcutaneously (3 million IU day-' at 8.00 p.m. 6 days a week for 4 weeks) or IL-2 plus MLT (40 mg day-' orally at 8.00 p.m. every day starting 7 days before IL-2). A complete response was obtained in 3/41 patients treated with IL-2 plus MLT and in none of the patients receiving IL-2 alone. A partial response was achieved in 8/41 patients treated with IL-2 plus MLT and in only 1/39 patients treated with IL-2 alone. Tumour objective regression rate was significantly higher in patients treated with IL-2 and MLT than in those receiving IL-2 alone (11/41 vs 1/39, P<0.001). The survival at 1 year was significantly higher in patients treated with IL-2 and MLT than in the IL-2 group (19/41 vs 6/39, P<0.05). Finally, the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone; on the contrary, the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone. The treatment was well tolerated in both groups of patients. This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy.

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.…”

Melatonin mediates seasonal adjustments in immune function

“…Melatonin also seems to boost the anti-tumor activities of IL-2 in humans with solid neoplasms [80].…”

Influence of dietary melatonin on photoreceptor survival in the rat retina: An ocular toxicity study

“…Previous studies (Bubenik and Purtill, 1980;Wiechmann and O'Steen, 1992;Sugawara et al, 1998) have suggested a potential detrimental effect of melatonin on photoreceptor cell survival in albino rats, and many reports suggest that melatonin may be beneficial for combating cancer, Lissoni et al, 1994), alleviating jet lag (Claustrat et al, 1992;Petrie et al, 1989) and entraining circadian rhythms (Petrie et al, 1989;Armstrong, 1989) such as sleep patterns (Reiter, 1980;Dollins et al, 1994). These perceived benefits have motivated many Americans to self-administer melatonin.…”