title: Immuno-chemotherapy of advanced colorectal cancer with alpha-2a interferon and 5-fluorouracil. Immunopharmacological studies.
abstract: Twelve patients with metastatic colorectal cancer received alternating cycles of low immunomodulating doses of alpha-IFN + 5-Fluorouracil (5-FU) or 5-FU alone. Hematological, biochemical and physical evaluation showed that both treatment cycles were well tolerated. However, transient fever and moderate flu-like symptoms were observed following alpha-IFN administration. Treatment with 5-FU alone produced long-lasting inhibition of CD8+ T lymphocytes, but did not depress NK activity (NKA). Combined treatment with alpha-IFN produced a short-term increase of NKA and antagonized the effect of 5-FU on CD8+ cells on day 5 of the cycle. Parallel studies on in vitro models showed antiproliferative effects of 5-FU on PHA-stimulated MNC and confirmed the preferential inhibition of CD8+ cells. Pretreatment with alpha-IFN did not reverse the effect of 5-FU on CD8+ lymphocytes, but partially protected MNC from the toxic effects of the drug. This was presumably due to the cytostatic effects induced by alpha-IFN on MNC before exposure to the cycle-specific antineoplastic agent. This investigation suggests that alpha-IFN could play a positive role in immuno-chemotherapy of colorectal cancer through multiple mechanisms not entirely related to direct antitumor effects of the agent.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, 2nd University of Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Filippi
authors.forename: G
authors.initials: G
authors.lastname: Cucchiara
authors.forename: S P
authors.initials: SP
authors.lastname: Prete
authors.forename: S
authors.initials: S
authors.lastname: Marini
authors.forename: F
authors.initials: F
authors.lastname: Ricci
authors.forename: C
authors.initials: C
authors.lastname: Nunziata
authors.forename: M
authors.initials: M
authors.lastname: Turriziani
authors.forename: E
authors.initials: E
authors.lastname: Bonmassar
authors.forename: M P
authors.initials: MP
authors.lastname: Fuggetta
authors.forename: L
authors.initials: L
authors.lastname: De Vecchis
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007167:Immunotherapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil