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Annals of Oncology 2:759-764, 1991
© 1991 European Society for Medical Oncology

research-article

Original article: Immuno-chemotherapy of advanced colorectal cancer with alpha-2a interferon and 5-fluorouracil. Immunopharmacological studies

R. De Filippi1,, G. Cucchiara2, S. P. Prete1, S. Marini1, E Ricci1, C. Nunziata1, M. Turriziani1, E. Bonmassar1, M. P. Fuggetta3 and L. De Vecchis1

1Department of Experimental Medicine and Biochemical Sciences 2nd University of Rome
2Division of Surgery1, Fatebenefratelli Hospital
3Institute of Experimental Medicine, National Council of Research (CNR) Rome, Italy

Correspondence to: Liana De Vecchis, MD Department of Experimental Medicine and Biochemical Sciences School of Medicine 2nd University of Rome Via O. Raimondo 00173 Rome, Italy

Twelve patients with metastatic colorectal cancer received alternating cycles of low immunomodulat-ing 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.

alpha-interferon, 5-FU, colorectal cancer, immuno-chemotherapy


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