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
P. Lissoni et al., 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, Oncology, 51(4), 1994, pp. 344-347
Our preliminary studies in humans have shown that the pineal neurohorm
one melatonin (MLT) may enhance the antitumor activity of IL-2, by con
firming the existence of a neuroendocrine control on cytokine effects.
On this basis, a study was started to evaluate the influence of a con
comitant administration of MLT and low-dose IL-2 in cancer patients, w
ho had progressed during a pre vious immunotherapy with IL-2 alone. Th
e study included 14 patients with advanced solid tumors (lung 6; kidne
y 4; stomach 2; liver 1; melanoma 1). IL-2 2 was given at a daily dose
of 3 million IU s.c. for 6 days/week for 4 weeks. MLT was given orall
y at a daily dose of 40 mg every day, starting 7 days prior to IL-2. O
bjective tumor regression, consisting of a partial remission (PR), was
achieved in 3/14 (21%) patients (lung 1; kidney 1; liver 1). Six othe
r patients had a stable disease (SD), while the remaining 5 cases prog
ressed. PR and SD were associated either with a significantly longer s
urvival at 1 year, or with a significantly higher increase in lymphocy
te and eosinophil mean number with respect to the patients with diseas
e progression. This preliminary study suggests that advanced solid neo
plasms resistant to IL-2 may become responsive to IL-2 therapy by a co
ncomitant administration of the pineal hormone MLT, which could act by
enhancing IL-2 antitumor immune effects and/or by increasing the susc
eptibility of cancer cells to the cytolysis mediated by IL- 2-induced
cytotoxic lymphocytes.