Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone.
Our preliminary studies in humans have shown that the pineal neurohormone melatonin (MLT) may enhance the antitumor activity of IL-2, by confirming the existence of a neuroendocrine control on cytokine effects. On this basis, a study was started to evaluate the influence of a concomitant administration of MLT and low-dose IL-2 in cancer patients, who had progressed during a previous immunotherapy with IL-2 alone. The study included 14 patients with advanced solid tumors (lung 6; kidney 4; stomach 2; liver 1; melanoma 1). IL-2 was given at a daily dose of 3 million IU s.c. for 6 days/week for 4 weeks. MLT was given orally at a daily dose of 40 mg every day, starting 7 days prior to IL-2. Objective tumor regression, consisting of a partial remission (PR), was achieved in 3/14 (21%) patients (lung 1; kidney 1; liver 1). Six other patients had a stable disease (SD), while the remaining 5 cases progressed. PR and SD were associated either with a significantly longer survival at 1 year, or with a significantly higher increase in lymphocyte and eosinophil mean number with respect to the patients with disease progression. This preliminary study suggests that advanced solid neoplasms resistant to IL-2 may become responsive to IL-2 therapy by a concomitant administration of the pineal hormone MLT, which could act by enhancing IL-2 antitumor immune effect and/or by increasing the susceptibility of cancer cells to the cytolysis mediated by IL-2-induced cytotoxic lymphocytes.
Lissoni
P
P
Division of Radiation Oncology, San Gerardo Hospital, Monza, Italy.
Barni
S
S
Cazzaniga
M
M
Ardizzoia
A
A
Rovelli
F
F
Brivio
F
F
Tancini
G
G
D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007958:Leukocyte Count; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D007376:Interleukin-2; D008550:Melatonin