Integrative Medicine > Melatonin  

Abstract

A randomized study of low-dose subcutaneous interleukin-2 plus melatonin versus supportive care alone in metastatic colorectal cancer patients progressing under 5-fluorouracil and folates

Barni S, Lissoni P, Cazzaniga M, Ardizzoia A, Meregalli S, Fossati V, Fumagalli L, Brivio F, Tancini G

Division of Radiation Oncology, San Gerardo Hospital, Monza, Italy

Chemotherapy with 5-fluorouracil (5-FU) and folates represents the first-line standard therapy for metastatic colorectal cancer, whereas at present there is no conventional second-time treatment.
Because of its importance in generating an effective anticancer immune response, interleukin-2 (IL-2) could constitute a new promising therapy of advanced colon cancer.
Generally, IL-2 may determine tumor regressions in colon cancer only when it is given at high toxic doses.
Our preliminary studies have shown that the pineal hormone melatonin may amplify IL-2 activity, which becomes active also at low doses in several tumor histotypes.
On the basis, we have performed a clinical trial to evaluate the impact of low-dose IL-2 plus melatonin on the survival time in metastatic colon cancer, which progressed in response to 5-FU plus folates.
The study included 50 metastatic colorectal cancer patients, who did not respond or progressed after initial response to first-line chemotherapy with 5-FU and folates.
Patients were randomized to receive supportive care alone or low-dose subcutaneous IL-2 (3 million IU/day for 6 days/week for 4 weeks) plus melatonin (40 mg/day orally).
No spontaneous tumor regression occurred in patients receiving supportive care alone.
A partial response was achieved in 3/25 patients treated with immunotherapy.
Percent survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with supportive care alone (9/25 vs. 3/25, p < 0.05).
This study suggests that low-dose subcutaneous IL-2 plus melatonin may be effective as a second-line therapy to induce tumor regression and to prolong percent survival at 1 year in metastatic colorectal cancer patients progressing under 5-FU and folates.

PMID: 7715908 [PubMed - indexed for MEDLINE]