title: 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.
abstract: 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.
authors.affiliation: Division of Radiation Oncology, San Gerardo Hospital, Monza, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Barni
authors.forename: P
authors.initials: P
authors.lastname: Lissoni
authors.forename: M
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoia
authors.forename: S
authors.initials: S
authors.lastname: Meregalli
authors.forename: V
authors.initials: V
authors.lastname: Fossati
authors.forename: L
authors.initials: L
authors.lastname: Fumagalli
authors.forename: F
authors.initials: F
authors.lastname: Brivio
authors.forename: G
authors.initials: G
authors.lastname: Tancini
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D013727:Terminal Care; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2; D005492:Folic Acid; D008550:Melatonin; D005472:Fluorouracil