title: Efficacy of repeated cycles of chemo-immunotherapy with thymosin alpha1 and interleukin-2 after intraperitoneal 5-fluorouracil delivery.
abstract: We have used chemo-immunotherapy with 5-fluorouracil (5-FU), thymosin alpha1 (T alpha1) and interleukin-2 (IL-2) to treat multiple liver metastases from colorectal cancer induced by DHD/K12 cells in syngeneic BDIX rats, comparing one and two cycles of treatment, and different treatment combinations. 5-FU was delivered loco-regionally as a continuous infusion via an intraperitoneal (i.p.) catheter from a subcutaneously implanted mini-pump, a method we developed for this study. We show here that two cycles of a triple chemo-immunotherapy regimen significantly increased the average survival time compared to one cycle, and compared to untreated controls or those treated with two cycles of 5-FU alone. At 150 days, two rats treated with two cycles of triple therapy were cured, showing no signs of cancer at autopsy; all the other rats died before this time. Triple chemo-immunotherapy resulted in significantly fewer extra-hepatic metastases than in the controls and in those treated with 5-FU only. Further, we found that two cycles of triple treatment significantly increased the absolute number of peripheral T cells expressing IL-2 receptor, CD4 and CD8 compared to controls. We conclude that two cycles of chemo-immunotherapy with 5-FU, T alpha1 and IL-2 were superior to one cycle of treatment and to other treatments tested. Our results suggest that the triple therapy acts by increasing numbers of effector T cells. This method shows promise for the use of multi-cycle chemo-immunotherapy in the treatment of unresectable metastases of colorectal cancer in humans.
authors.affiliation: VII Patologia Chirurgica, Università La Sapienza, Roma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Silecchia
authors.forename: E
authors.initials: E
authors.lastname: Guarino
authors.forename: P
authors.initials: P
authors.lastname: Sinibaldi-Vallebona
authors.forename: P
authors.initials: P
authors.lastname: Pierimarchi
authors.forename: A
authors.initials: A
authors.lastname: Restuccia
authors.forename: E
authors.initials: E
authors.lastname: Spaziani
authors.forename: P
authors.initials: P
authors.lastname: Bernard
authors.forename: C
authors.initials: C
authors.lastname: Tuthill
authors.forename: E
authors.initials: E
authors.lastname: Garaci
authors.forename: G
authors.initials: G
authors.lastname: Rasi
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D005472:Fluorouracil / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000032:analysis; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013947:Thymosin; D005472:Fluorouracil; D000077596:Thymalfasin