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. 1999 May;80(5-6):786–791. doi: 10.1038/sj.bjc.6690422

A randomized phase II trial of 5-fluorouracil, with or without human interferon-β, for advanced colorectal cancer

A Villar-Grimalt 1, M T Candel 1, B Massuti 2, J Lizón 3, B Sánchez 3, A Frau 4, B Gorostidi 5, R Goedkoop 6
PMCID: PMC2362283  PMID: 10360656

Abstract

This study compared the efficacy and safety of 5-fluorouracil (5-FU) monotherapy to that of 5-FU combined with natural human interferon-β (IFN-β) in patients with unresectable, advanced colorectal carcinoma. Forty-nine chemotherapy-naive patients were randomized to 5-FU alone or to the combination. All patients received 750 mg m−2 day−1 5-FU for 5 days by continuous intravenous (i.v.) infusion, followed after day 15 by a weekly i.v. bolus of 750 mg m−2. IFN-β was injected intramuscularly three times weekly at 9 M IU. Treatment continued for 52 weeks, or until disease progression or intolerable toxicity. Clinical endpoints were tumor response, time to progression, survival and toxicity. The addition of IFN-β to 5-FU significantly improved response rate (33.3% vs 4.5% for evaluable patients; P = 0.021), time to progression (median 7.2 vs 4.2 months; P = 0.0435), and survival time (median 15.9 vs 7.2 months; P = 0.038) without significantly increasing toxicity compared to 5-FU alone. Cumulative 5-FU dose was higher with combined therapy (P < 0.001): more patients receiving monotherapy discontinued treatment because of disease progression. Fever was more frequent with combined therapy (P = 0.008); there were no other differences in toxicity. The only grade IV toxicity observed was neutropenia (two patients per group). A randomized phase III trial has been initiated to confirm the synergy between 5-FU and IFN-β. © 1999 Cancer Research Campaign

Keywords: colorectal cancer, 5-fluorouracil, interferon-β, synergism, survival

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Selected References

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  1. Beard C. M., Spencer R. J., Weiland L. H., O'Fallon W. M., Melton L. J., 3rd Trends in colorectal cancer over a half century in Rochester, Minnesota, 1940 to 1989. Ann Epidemiol. 1995 May;5(3):210–214. doi: 10.1016/1047-2797(94)00107-5. [DOI] [PubMed] [Google Scholar]
  2. Borden E. C., Hogan T. F., Voelkel J. G. Comparative antiproliferative activity in vitro of natural interferons alpha and beta for diploid and transformed human cells. Cancer Res. 1982 Dec;42(12):4948–4953. [PubMed] [Google Scholar]
  3. Carter S. K. Editorial: Large-bowel cancer-The current status of treatment. J Natl Cancer Inst. 1976 Jan;56(1):3–10. doi: 10.1093/jnci/56.1.3. [DOI] [PubMed] [Google Scholar]
  4. Dufour P., Husseini F., Dreyfus B., Cure H., Martin C., Prevost G., Olivier J. P., Dumas F., Duclos B., Olivares R. 5-Fluorouracil versus 5-fluorouracil plus alpha-interferon as treatment of metastatic colorectal carcinoma. A randomized study. Ann Oncol. 1996 Aug;7(6):575–579. doi: 10.1093/oxfordjournals.annonc.a010673. [DOI] [PubMed] [Google Scholar]
  5. Erlichman C., Fine S., Wong A., Elhakim T. A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. J Clin Oncol. 1988 Mar;6(3):469–475. doi: 10.1200/JCO.1988.6.3.469. [DOI] [PubMed] [Google Scholar]
  6. Greco F. A., Figlin R., York M., Einhorn L., Schilsky R., Marshall E. M., Buys S. S., Froimtchuk M. J., Schuller J., Schuchter L. Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer. J Clin Oncol. 1996 Oct;14(10):2674–2681. doi: 10.1200/JCO.1996.14.10.2674. [DOI] [PubMed] [Google Scholar]
  7. HEIDELBERGER C., CHAUDHURI N. K., DANNEBERG P., MOOREN D., GRIESBACH L., DUSCHINSKY R., SCHNITZER R. J., PLEVEN E., SCHEINER J. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 1957 Mar 30;179(4561):663–666. doi: 10.1038/179663a0. [DOI] [PubMed] [Google Scholar]
  8. Hill M., Norman A., Cunningham D., Findlay M., Nicolson V., Hill A., Iveson A., Evans C., Joffe J., Nicolson M. Royal Marsden phase III trial of fluorouracil with or without interferon alfa-2b in advanced colorectal cancer. J Clin Oncol. 1995 Jun;13(6):1297–1302. doi: 10.1200/JCO.1995.13.6.1297. [DOI] [PubMed] [Google Scholar]
  9. Jäger E., Heike M., Bernhard H., Klein O., Bernhard G., Lautz D., Michaelis J., Meyer zum Büschenfelde K. H., Knuth A. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J Clin Oncol. 1996 Aug;14(8):2274–2279. doi: 10.1200/JCO.1996.14.8.2274. [DOI] [PubMed] [Google Scholar]
  10. Kemeny N., Younes A., Seiter K., Kelsen D., Sammarco P., Adams L., Derby S., Murray P., Houston C. Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity. Cancer. 1990 Dec 15;66(12):2470–2475. doi: 10.1002/1097-0142(19901215)66:12<2470::aid-cncr2820661205>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  11. Köhne C. H., Wilke H., Hecker H., Schöffski P., Käufer C., Rauschecker H., Andreesen R., Ohl U., Lange H. J., Klaassen U. Interferon-alpha does not improve the antineoplastic efficacy of high-dose infusional 5-fluorouracil plus folinic acid in advanced colorectal cancer. First results of a randomized multicenter study by the Association of Medical Oncology of the German Cancer Society (AIO). Ann Oncol. 1995 May;6(5):461–466. doi: 10.1093/oxfordjournals.annonc.a059216. [DOI] [PubMed] [Google Scholar]
  12. Leichman C. G., Fleming T. R., Muggia F. M., Tangen C. M., Ardalan B., Doroshow J. H., Meyers F. J., Holcombe R. F., Weiss G. R., Mangalik A. Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study. J Clin Oncol. 1995 Jun;13(6):1303–1311. doi: 10.1200/JCO.1995.13.6.1303. [DOI] [PubMed] [Google Scholar]
  13. Moertel C. G. Clinical management of advanced gastrointestinal cancer. Cancer. 1975 Aug;36(2):675–682. doi: 10.1002/1097-0142(197508)36:2+<675::aid-cncr2820360810>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  14. Pazdur R., Ajani J. A., Patt Y. Z., Winn R., Jackson D., Shepard B., DuBrow R., Campos L., Quaraishi M., Faintuch J. Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma. J Clin Oncol. 1990 Dec;8(12):2027–2031. doi: 10.1200/JCO.1990.8.12.2027. [DOI] [PubMed] [Google Scholar]
  15. Platanias L. C., Uddin S., Colamonici O. R. Tyrosine phosphorylation of the alpha and beta subunits of the type I interferon receptor. Interferon-beta selectively induces tyrosine phosphorylation of an alpha subunit-associated protein. J Biol Chem. 1994 Jul 8;269(27):17761–17764. [PubMed] [Google Scholar]
  16. Poon M. A., O'Connell M. J., Moertel C. G., Wieand H. S., Cullinan S. A., Everson L. K., Krook J. E., Mailliard J. A., Laurie J. A., Tschetter L. K. Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol. 1989 Oct;7(10):1407–1418. doi: 10.1200/JCO.1989.7.10.1407. [DOI] [PubMed] [Google Scholar]
  17. Schwartz E. L., Baptiste N., Wadler S., Makower D. Thymidine phosphorylase mediates the sensitivity of human colon carcinoma cells to 5-fluorouracil. J Biol Chem. 1995 Aug 11;270(32):19073–19077. doi: 10.1074/jbc.270.32.19073. [DOI] [PubMed] [Google Scholar]
  18. Taniguchi T., Mantei N., Schwarzstein M., Nagata S., Muramatsu M., Weissmann C. Human leukocyte and fibroblast interferons are structurally related. Nature. 1980 Jun 19;285(5766):547–549. doi: 10.1038/285547a0. [DOI] [PubMed] [Google Scholar]
  19. Wadler S., Schwartz E. L., Goldman M., Lyver A., Rader M., Zimmerman M., Itri L., Weinberg V., Wiernik P. H. Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma. J Clin Oncol. 1989 Dec;7(12):1769–1775. doi: 10.1200/JCO.1989.7.12.1769. [DOI] [PubMed] [Google Scholar]
  20. Wong V. L., Rieman D. J., Aronson L., Dalton B. J., Greig R., Anzano M. A. Growth-inhibitory activity of interferon-beta against human colorectal carcinoma cell lines. Int J Cancer. 1989 Mar 15;43(3):526–530. doi: 10.1002/ijc.2910430331. [DOI] [PubMed] [Google Scholar]

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