Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. A phase II study

Abstract

Background. Numerous attempts to identify active cytotoxic agents for the treatment of metastatic renal cell carcinoma (RCC) have proved disappointing. However, several recent developments in biologic therapy of neo‐plastic disease have substantially improved the prospects for the treatment of advanced RCC. Melatonin (MLT), a hormone regulated by the pineal gland, has been shown to act on the immune system by causing the release of cytokines from activated T‐cell populations. Methods. A series of 22 patients with documented progressing RCC entered a trial in which the authors studied the effect of a long term regimen (12 months) with human lymphoblastoid interferon (IFN), 3 mega units (MU) intramuscularly 3 times per week, and MLT, 10 mg orally every day. Results. Twenty‐one patients were evaluable for response and toxicity. There were seven remissions (33%): three complete, involving lung and soft tissue and four partial, with a median duration at the time of this writing of 16 months. Nine patients achieved stable disease, and five progressed. General toxicity was mild. Fever, chills, arthralgias, and myalgias occurred rarely. Leukopenia and hepatic enzyme elevation were modest and always reversible. Conclusions. Response rate and toxic effects observed during this study warrant additional randomized studies to define the role of MLT's concomitant administration in the clinical response to IFN in metastatic RCC. Cancer 1994; 73:3015–9.

The therapeutic application of melatonin in supportive care and palliative medicine

“…Leukopenia and elevation of liver enzymes are modest and reversible. 39 Other possible adverse affects include inhibition of fertility, suppression of male sexual drive, hypothermia, headache, nausea, nightmares, or worsened depression. 99 No serious adverse side effects were reported after oral administration of high dose melatonin (1 g/d) for 30 days in healthy humans.…”

Melatonin in Cancer Management: Progress and Promise

“…There were a total of seven (33%) remissions: four complete (involving lung and soft tissue) and four partial, with a median duration of 16 months. Nine patients achieved stable disease, and five progressed (22). The response rate observed in this study definitely warrants additional trials to determine the usefulness of concomitant administration of melatonin in the clinical response to IFN in metastatic RCC (22).…”

“…Neri et al (22) conducted a trial in 22 patients with documented progressing RCC. In this study, the authors assessed the effect of a long-term regimen (12 months) with human lymphoblastoid IFN and melatonin on RCC.…”

Intervention in the aging immune system: Influence of dietary restriction, dehydroepiandrosterone, melatonin, and exercise

“…Hence, the observation that neoplasia is associated with low circulatory levels of MLT has offered a rationale for a therapeutic intervention, and a number of recent studies have demonstrated that MLT therapy suppresses cancer growth (reviewed in ref 133,135). Several clinical studies have shown that MLT therapy, alone or in combination with IL-2, significantly decreases the progression of various tumors, e.g., carcinomas (136), melanoma (135), renal (133,135), lung (135)(136)(137)(138), and breast tumors (139)(140)(141). Cancer patients, who were unable to tolerate the IL-2 therapy alone and who did not respond to standard anti-cancer chemotherapies, were shown to have increased IL-2 tolerance, and they exhibited an effective antitumor defense response when they were treated with a combination of MLT and IL-2 (134,135,(142)(143)(144)(145)(146)(147)(148).…”