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Clinical Studies of the Modulation of Ftorafur

  • Patrick J. Creaven
  • Youcef M. Rustum
  • Nicholas J. Petrelli
  • Vera A. Gorbunova
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 339)

Abstract

Biochemical modulation of fluoropyrimidines has now been evaluated clinically for more than a decade in the treatment of colorectal carcinoma and more recently in other tumors. Although real progress has been made in terms of increased response rate13 there has been little, if any, effect on survival. Several approaches have been used in an attempt to improve on response rates and impact on survival with fluoropyrimidine modulation. Some of these are listed in Table 1.

Keywords

Colorectal Carcinoma Folinic Acid Pyrimidine Nucleoside Roswell Park Cancer Institute Metastatic Colorectal Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    N. Petrelli, H.O. Douglass, Jr., L. Herrera, D. Russell, D.M. Stablein, H.W., et al. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: A prospective randomized phase III trial. J. Clin. Oncol. 7: 1419–1426, 1989.PubMedGoogle Scholar
  2. 2.
    P.J. Creaven. 5-Fluorouracil and folinic acid: Summary of clinical experience, in: “The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy,” Y. Rustum, J.J. McGuire, eds., Plenum Press, New York and London 1988, pp. 303–311.CrossRefGoogle Scholar
  3. 3.
    Advanced Colorectal Cancer Meta-Analysis Project. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate. J. Clin. Oncol. 10: 896–903, 1992.Google Scholar
  4. 4.
    T.M. Loffler, F.W. Weber and T.U. Hausamen. Protracted continuous-infusion 5-fluorouracil with intermittent high-dose leucovorin in advanced and metastatic colorectal cancer: A pilot study. in “Leucovorin Modulation of Fluoropyrimidines: A New Frontier in Cancer Chemotherapy,” H.M. Pinedo, Y.M. Rustum, eds., Royal Society of Medicine Services Limited, London and New York 1989, pp. 65–68.Google Scholar
  5. 5.
    B. Ardalan, L. Chua, E. Tian, R. Reddy, K. Sridhar, et al. A phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma. J. Clin. Oncol. 9: 625–630, 1991.PubMedGoogle Scholar
  6. 6.
    P.J. Creaven, Y.M. Rustum, N.J. Petrelli, M. Rodriguez, C. Frank and J.K. Solomon. A pharmacokinetically directed phase I/II study of 5-fluorouracil/high dose leucovorin in colorectal carcinoma resistant to standard doses. Proc. Am. Assoc. Cancer Res., 33: 218, 1992.Google Scholar
  7. 7.
    E.M. Newman, S.A. Akman, J.S. Harrison, L.A. Leong, K.A. Margolin, et al. Pharmacokinetics and toxicity of continuous infusion (6S)-folinic acid and bolus 5-fluorouracil in patients with advanced cancer. Cancer Res. 52: 2408–2412, 1992.PubMedGoogle Scholar
  8. 8.
    D. Machover, X. Grison, E. Goldschmidt, J. Zittoun, J-P. Lotz, et al. Fluorouracil combined with the pure (6S)-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: A phase I-II study. J. Natl. Cancer Inst. 84: 321–327, 1992.PubMedCrossRefGoogle Scholar
  9. 9.
    P.J. Creaven, N. Petrelli, Y.M. Rustum, L. Herrera, J.W. Cowens, et al. Phase I study of 6S-leucovorin and 5-fluorouracil in colorectal carcinoma. Proc. Am. Assoc. Cancer Res. 32: 174, 1991.Google Scholar
  10. 10.
    B. Ardalan, G. Singh, H. Silberman. A randomized phase I and II study of short-term infusion of high-dose fluorouracil with or without N-(phosphonacetyl)-L-aspartic acid in patients with advanced pancreatic and colorectal cancers. J. Clin. Oncol. 6: 1053–1058, 1988.Google Scholar
  11. 11.
    S. Wadler, B. Lembersky, M. Atkins, J. Kirkwood and N. Petrelli. Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: An Eastern Cooperative Oncology Group Study. J. Clin. Oncol. 9: 1806–1810, 1991.PubMedGoogle Scholar
  12. 12.
    L.V. Manzuik, N.I. Perevodchikova, V.A. Gorbunova, AS. Singin, G.C. Gerasimova, et al. Initial clinical experience with oral ftorafur and oral 6R, S-leucovorin in advanced colorectal carcinoma. Proc. Am. Soc. Clin. Oncol. 11: 119, 1992.Google Scholar
  13. 13.
    D. Raminski, P.J. Creaven, Y.M. Rustum, S. Perrapato, R. Huben, et al. Phase I clinical trial of floxuridine with leucovorin in patients with advanced genitourinary cancer. Proc. Am. Soc. Clin. Oncol. 11: 206, 1992.Google Scholar
  14. 14.
    D. Spicer, F. Muggia, A. Tulpule, K. Chan, G. Leichman, et al. Phase I circadian dosing of daily oral uracil plus 1-(tetrahydro-2-furanyl)-5-fluorouracil with leucovorin. Proc. Am. Soc. Clin. Oncol. 10: 118, 1991.Google Scholar
  15. 15.
    F.M. Muggia, S. Jeffers, C.G. Leichman, A. Tulpule, R. Hanisch, et al. Potential for uracil + ftorafur to mimic protracted infusions of 5-fluorouracil. Proc. Am. Soc. Clin. Oncol. 11: 135, 1992.Google Scholar
  16. 16.
    R. Pazdur, D.H. Ho, Y. Lassere, B. Bready, I.H. Krakoff, et al. Phase I trial of oral ftorafor and uracil. Proc. Am. Soc. Clin. Oncol. 11: 111, 1992.Google Scholar
  17. 17.
    Y.M. Rustum, P.J. Creaven and N.J. Petrelli. Clinical pharmacokinetics of a uracil-ftorafur combination in patients with advanced solid tumors. Proc. Am. Soc. Clin. Oncol. 11: 110, 1992.Google Scholar
  18. 18.
    S. Hillers, R.A. Zhuk and M. Lidaks. Analogs of pyrimidine nucleosides. I. N-(α-furanidyl) derivatives of natural pyrimidine bases and their antimetabolites. Dokl. Akad. Nauk SSSR 176: 332–335, 1967.Google Scholar
  19. 19.
    M.A. Friedman and R.J. Ignoffo. A review of the United States clinical experience of the fluoropyrimidine, ftorafur (NAC-148958). Cancer Treatment Reviews 7: 205–213, 1980.PubMedCrossRefGoogle Scholar
  20. 20.
    N.G. Blokhina, E.K. Vozny and A.M. Garin. Results of treatment of malignant tumors with ftorafur. Cancer 30: 390–392, 1972.PubMedCrossRefGoogle Scholar
  21. 21.
    M.I. Anttila, E.A. Sotaniemi, M.I. Kairaluoma, R.E. Mokka and H.T. Sandquist. Pharmacokinetics of ftorafur after intravenous and oral administration. Cancer Chemother. Pharmacol. 10: 150–153, 1983.Google Scholar
  22. 22.
    C.L. Hornbeck, J.C. Griffiths, R.A. Floyd, N.C. Ginther, J.E. Byfield, et al. Serum concentrations of 5-FU, ftorafur and a major serum metabolite following ftorafur chemotherapy. Cancer Treat. Rep. 65: 69–72, 1981.PubMedGoogle Scholar
  23. 23.
    J.L. Au, A.T. Wu, M.A. Friedman and W. Sadee. Pharmacokinetics and metabolism of ftorafur in man. Cancer Treat. Rep. 63: 343–350, 1979.PubMedGoogle Scholar
  24. 24.
    Y.M. El Sayed and W. Sadee. Metabolic activation of R, S-l-(tetrahydro-2-furanyl)-5-furorouracil (ftorafur) to 5-fluorouracil by soluble enzymes. Cancer Res. 43: 4039–4044, 1983.PubMedGoogle Scholar
  25. 25.
    G.A. Belitsky, V.M. Bukhman and I.A. Konopleva. Changes in toxic and antitumor properties of ftorafur by induction or inhibition of the microsomal enzyme activity. Cancer Chemother. Pharmacol. 6: 183–187, 1981.PubMedCrossRefGoogle Scholar
  26. 26.
    S. Fujii, K. Ikrenaka, M. Fukushima and T. Shirasaka. Effect of uracil and its derivatives on antitumor activity of 5-fluorouracil and l-(2-tetrahydrofuryl)-5-tluorouracil. Gann 69: 763–772, 1978.PubMedGoogle Scholar
  27. 27.
    S. Fujii, S. Kitano, K. Ikenaka and T. Shirasaka. Effect of coadministration of uracil or cytosine on the antitumor activity of clinical doses of l-(2-tetrahydrofuryl)-5-fluorouracil and level of 5-fluorouracil in rodents. Gann 70: 209–214, 1979.PubMedGoogle Scholar
  28. 28.
    K. Ota, T. Taguchi and K. Kimura. Report on nationwide pooled data and cohort investigation in UFT phase II study. Cancer Chemothera. Pharmacol. 22: 333–338, 1988.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Patrick J. Creaven
    • 1
  • Youcef M. Rustum
    • 2
  • Nicholas J. Petrelli
    • 3
  • Vera A. Gorbunova
    • 4
  1. 1.Division of Investigational TherapeuticsMoscowRussia
  2. 2.Department of MedicineDepartment of Experimental TherapeuticsMoscowRussia
  3. 3.Department of SurgeryRoswell Park Cancer Institute (RPCI)BuffaloMoscowRussia
  4. 4.Cancer Research Center (CRC) RAMSMoscowRussia

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