Abstract
Recent advances in our knowledge of psychoneuroimmune interactions involved in the control of tumour growth have shown the possibility of manipulating host anticancer defences through a neuroimmunotherapeutic strategy. In particular, our previous studies have demonstrated that the concomitant administration of the pineal neurohormone melatonin may amplify the antitumour efficacy of interleukin-2 (IL-2) in humans. On this basis, a study was planned to investigate the influence of neuroimmunotherapy with low-dose IL-2 plus melatonin on survival time and on performance status in untreatable metastatic cancer patients. The study included 100 patients with metastatic solid tumours, for whom no standard therapy was available. They were randomized to receive IL-2 (3 x 106 IU/day subcutaneously for 4 weeks) plus melatonin (40 mg/day orally) or supportive care alone. Partial tumour regressions were seen in 9/52 (17%) patients treated with the immunotherapy, and in none of the patients treated with supportive care alone. The percentage of survival at 1 year was significantly higher in patients treated with IL-2 and melatonin than in those receiving the supportive care alone (21/52 versus 5/48, P<0.005). Moreover, the performence status improved in 22/52 patients of the immunotherapy group and in only 8.48 patients treated with supportive care (P<0.01). This study shows that cancer neuroimmunotherapy with low-dose IL-2 and the pineal hormone melatonin may prolong the survival time and improve the quality of life of patients with metastatic solid tumours who do not respond to conventional therapies.
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References
Atzpodien J, Kirchner H (1990) Cancer, cytokines, and cytotoxic cells: interleukin-2 in the immunotherapy of human neoplasms. Klin Wochenschr 68:1–11
Atzpodien J, Korfer A, Franks CR, Poliwoda H, Kirchner H (1990) Home therapy with recombinant interleukin-2 and interferon-alpha 2β in advanced human malignancies. Lancet I:1509–1512
Chouaib S, Fradelizi D (1982) The mechanism of inhibition of human IL 2 production. J Immunol 129:2463–2467
Lissoni P, Barni S, Paolorossi F, et al (1987) Evidence for altered opioid activity in patients with cancer. Br J Cancer 56:834–837
Lissoni P, Barni S, Archili C, et al (1990) Endocrine effects of a 24-hour intravenous infusion of interleukin-2 in the immunotherapy of cancer. Anticancer Res 10:753–758
Lissoni P, Barni S, Tancini G, et al (1994) A randomized 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. Br J Cancer 69:196–199
Maestroni GJM, Conti A, Pierpaoli W (1986) Role of the pineal gland in immunity. J Neuroimmunol 13:19–26
Plotnikoff NP, Miller GC (1983) Enkephalins as immunomodulators. Int J Immunopharmacol 5:437–442
Regelson W, Pierpaoli W (1987) Melatonin: a rediscovered antitumor hormone? Cancer Invest 5:379–385
Rosenberg SA, Lotze MT, Muul LM, et al (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316:889–897
Stein RC, Malkovska V, Morgan S, et al (1991) The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2. Br J Cancer 63:275–278
Wanebo HJ, Pace R, Hargett S, Katz D, Sando J (1986) Production of and response to interleukin-2 in peripheral blood lymphocytes of cancer patients. Cancer 57:656–662
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Lissoni, P., Barni, S., Fossati, V. et al. A randomized study of neuroimmunotherapy with low-dose subcutaneous interleukin-2 plus melatonin compared to supportive care alone in patients with untreatable metastatic solid tumour. Support Care Cancer 3, 194–197 (1995). https://doi.org/10.1007/BF00368890
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DOI: https://doi.org/10.1007/BF00368890