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.
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.
Lissoni
Paolo
P
Division of Radiation Oncology, S. Gerardo Hospital, Monza, Italy. p.lissoni@hsgerardo.org
Brivio
Fernando
F
Fumagalli
Luca
L
Messina
Giusy
G
Vigoré
Luigi
L
Parolini
Daniela
D
Colciago
Massimo
M
Rovelli
Franco
F
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*
D007376:Interleukin-2; D008550:Melatonin