title: Neuroimmunomodulation in medical oncology: application of psychoneuroimmunology with subcutaneous low-dose IL-2 and the pineal hormone melatonin in patients with untreatable metastatic solid tumors.
abstract: BACKGROUND
  Anticancer immunity is under psychoneuroendocrine regulation, mainly via the pineal gland and brain opioid system, which may stimulate and inhibit antitumor immunity respectively. Cancer-related immuno-suppression does not depend only on functional damage of immune cells, but also on alterations of systems responsible for the neuroimmunomodulation, the most frequent of wich is a decline in blood levels of the pineal hormone melatonin (MLT).
  
  
  METHODS
  A study was performed to evaluate the influence of an exogenous administration of MLT alone or MLT plus subcutaneous (SC) low-dose interleukin-2 on tumor progression and survival time in patients with untreatable metastatic solid tumors. The study included 846 patients with metastatic solid tumor (non-small cell lung cancer or gastrointestinal tract tumors) randomized to receive the best supportive care only, supportive care plus MLT (20 mg/day, orally in the evening), or MLT plus SC low-dose IL-2 (3 MIU/day for 5 days/week, for 4 consecutive weeks).
  
  
  RESULTS
  The MLT alone was able to induce a significant increase of disease stabilization and survival time with respect to supportive care alone. The association of lL-2 with MLT provided a further improvement in the percentage of tumor regressions and of 3-year survival with respect to MLT alone.
  
  
  CONCLUSIONS
  The administration of IL-2 and the pineal hormone MLT may induce control of neolplastic growth and a prolonged survival time in patients with metastatic solid tumors, for whom no other conventional anticancer therapy is available.
authors.affiliation: Division of Radiation Oncology, S. Gerardo Hospital, Monza, Italy. p.lissoni@hsgerardo.org
authors.forename: Paolo
authors.initials: P
authors.lastname: Lissoni
authors.forename: Fernando
authors.initials: F
authors.lastname: Brivio
authors.forename: Luca
authors.initials: L
authors.lastname: Fumagalli
authors.forename: Giusy
authors.initials: G
authors.lastname: Messina
authors.forename: Luigi
authors.initials: L
authors.lastname: Vigoré
authors.forename: Daniela
authors.initials: D
authors.lastname: Parolini
authors.forename: Massimo
authors.initials: M
authors.lastname: Colciago
authors.forename: Franco
authors.initials: F
authors.lastname: Rovelli
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care / Q000379:methods*
chemical_list: D007376:Interleukin-2; D008550:Melatonin