Advertisement

Folinic Acid (CF)/5-Fluorouracil (FUra) Combinations in Advanced Gastrointestinal Carcinomas

  • Hansjochen Wilke
  • H.-J. Schmoll
  • P. Preusser
  • U. Fink
  • M. Stahl
  • C. Schöber
  • H. Link
  • M. Freund
  • A. Hanauske
  • H.-J. Meyer
  • W. Achterrath
  • H. Poliwoda
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 131)

Abstract

The introduction of CF promises to be an important step towards a more successful treatment of colorectal cancer. CF (CH2-H4Pte Glu) is a biochemical modulator of fluoropyrimidine action and enhances cytotoxicity of FUra and FUDR in vitro and in vivo. CF/FUra combinations have been investigated in a number of clinical trials. Objective response rates of 30% – 40% were reproducibly achieved indicating a superiority of CF/FUra over FUra alone (1–7). However, inspite of these promising results the benefit of chemotherapy in colorectal cancer remains undetermined with respect to patient survival which is influenced by factors leading to a wide range of spontaneous survival time of patients with advanced colorectal cancer, e.g. stage of disease, tumor load, and particularly rate of tumor growth at time of diagnosis. If tumor growth rates are not determined prior to therapy treatment outcome might be biased by slowly or rapidly proliferating tumors and not necessarily reflect drug activity. Also, lack of tumor growth during observation period might be misinterpreted as antineoplastic effect (“no change”,“stabilisation”).

Keywords

Gastric Cancer Advanced Gastric Cancer Objective Response Rate Folinic Acid Advanced Colorectal Cancer 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Laufman, L.R., Krzeczowski, K.A., Roach, R, and Segal, M., 1987, Leucovorin plus 5-Fluorouracil: an effective treatment for metastatic colon cancer, J. Clin. Oncol., 5: 1394–1400.PubMedGoogle Scholar
  2. 2.
    Cunningham, J., Bukowski, R.M., Budd, T.G., Weick, J.K., and Purvis, J., 1984, 5-fluorouracil and folinic acid: a phase i-II trial in gastrointestinal malignancy, Investigational New Drugs, 2: 391 – 395.Google Scholar
  3. 3.
    Machover, D., Goldschmidt, E., Chollet, P., Metzger, G., Zittoun, J., Marquet, J., Vandenbulcke, J.M., Misset, J.L., Schwarzenberg, L., Fourtillan, J.B., Gaget, H., and Mathé, G., 1986, Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high dose folinic acid, J. Clin. Oncol., 4: 685–696.PubMedGoogle Scholar
  4. 4.
    Zakem, M., Hines, J.D., Adelstein, D.J., and Rustum, Y.M., 1986, High-dose leukovorin and 5-fluorouracil (5-FU) in refractory and relapsed colo-rectal carcinoma, Proc. Am. Soc. Clin. Oncol., 5: 81 (abstr.).Google Scholar
  5. 5.
    Doroshow, J.H., Bertrand, M., Multhauf, P., Leong, L., Goldberg, D., Margolin, K., Carr, B., Akman, S., and Hill, R., 1987, Prospective randomized trial comparing 5-fluorouracil versus (vs) 5-FU and high dose folinic acid (HDFA) for treatment of advanced colorectal cancer. Proc. Am. Soc. Clin. Oncol., 6: 96 (abstr.).Google Scholar
  6. 6.
    Petrelli, N., Herrera, L., Stulc, J., Rustum, Y.M., and Mittelman, A., 1987, A phase III study of 5-fluorouracil (5-FU) versus 5-FU + methotrexate (MTX) versus 5-FU + high dose leucovorin (CF) in metastatic colorectal adenocarcinoma. Proc. Am. Soc. Clin. Oncol., 6: 74 (abstr.).Google Scholar
  7. 7.
    Ehrlichman, C., Fine, S., Wong, A., et al., 1988, A randomized trial of 5-fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. J. Clin. Oncol., in press.Google Scholar
  8. 8.
    Carter, S.D., 1976, Large bowel cancer: the current status of treatment, JNCI, 56: 3 – 10.PubMedGoogle Scholar
  9. 9.
    Moertel, C.G., 1978, Chemotherapy of gastrointestinal cancer, N. Engl. J. Med., 299: 1049–1052.PubMedCrossRefGoogle Scholar
  10. 10.
    Radice, P.A., Bunn, P.A., and Ihde, D.C., 1979, Therapeutic trials with VP-16–213 and VM-26: active agents in small cell lung cancer, non-hodgkin’s lymphomas, and other malignancies. Cancer Treat. Rep., 63: 1231–1239.PubMedGoogle Scholar
  11. 11.
    Schmoll, H.-J., Niederle, N., and Achterrath, W., 1981, Etoposid (VP-16–213). Klin. Wochenschrift, 59: 1177–1188.CrossRefGoogle Scholar
  12. 12.
    Dorr, R.T., and Fritz, W.L.,1980,5-Fluorouracil,in:“Cancer chemotherapy handbook,” R.T. Dorr, and W.L. Fritz, eds., Elsevier, New York, Amsterdam, Oxford.Google Scholar
  13. 13.
    Cocconi, G., DeLisi, V., and Blasio, B., 1982, Randomized comparison of 5-FU alone or combined with mitomycin and cytarabine (MFC) in the treatment of advanced gastric cancer. Cancer Treat. Rep., 66: 1263–1266.PubMedGoogle Scholar
  14. 14.
    MacDonald, J.S., Gunderson, L.L.,and Cohn I.Jr., 1985, Cancer of the stomach, in: Cancer, principles and practise of oncology, V. T. DeVita, S. Hellman, and S.A. Rosenberg, eds., Lippincott, Philadelphia.Google Scholar
  15. 15.
    Kelsen, D.p., Magill, G., and Cheng, E., Phase II trial of Etoposide (VP-16) in the treatment of upper gastrointestinal malignancies. Proc. Am. Soc. Clin. Oncol.,123: 96 (abstr.)Google Scholar
  16. 16.
    Hill, B.T., 1986, Potential of continous tumor cell lines for establishing patterns of cross-resistance and collateral sensitivity in vitro, Drugs Exptl. Clin. Res., 12: 685–696.Google Scholar
  17. 17.
    Osswaldt, H., and Kunz, W., 1987, Therapeutic synergism of Etoposide and 5-fluorouracil combined sequentially in advanced leukemia L 1210, Cancer Res. Clin. Oncol., 113 (suppl.): 53 (abstr.)Google Scholar
  18. 18.
    Beretta, G., Fraschini,P., Labianca, R., Arnoldi, E., Pan-cera, G., Tedeschi, L., and Luporini, G., 1986, Weekly 5fluorouracil (F) versus combination chemotherapy for advanced gastrointestinal carcinomas, Proc. Am. Soc. Clin. Oncol., 5: 94 (abstr.).Google Scholar
  19. 19.
    Douglass, H.O.Jr., Lavin, P.T., Goudsmit, A., Klaasen, D. J., and Paul, A.R., 1984, An eastern cooperative oncology group evaluation of combinations of methyl-CCNU, mitomycin C, adriamycin, and 5-fluorouracil in advanced measurable gastric cancer (EST 2277 ), J. Clin. Oncol., 2: 1372–1381.Google Scholar
  20. 20.
    MacDonald, J.S., Schein, P.S., Wooley, P.V., Smythe, T., Ueno, W., Hoth, D., Smith, F., Boiron, M., Gisselbrecht, C., Brunet, R., and Lagarde, C., 1980, 5-Fluorouracil, doxorubicin, and mitomycin ( FAM) combination-chemotherapy for advanced gastric cancer, Ann. Int. Med., 93: 533–536.PubMedGoogle Scholar
  21. 21.
    Fornasiero, A., Cartei, G., Daniele, O., Fosser, V., and Fiorentino, M. V., 1984, FAM2 regimen in disseminated gastric cancer, Tumori, 70: 77 – 80.PubMedGoogle Scholar
  22. 22.
    MacDonald. J.S., Gunderson, L.L., and Cohn, I.Jr., 1985, Cancer of the stomach, in: Cancer, principles and practise of oncology, V. T. DeVita, S. Hellman, and S.A. Rosenberg, eds., Lippincott, Philadelphia.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Hansjochen Wilke
    • 1
  • H.-J. Schmoll
    • 1
  • P. Preusser
    • 1
  • U. Fink
    • 1
  • M. Stahl
    • 1
  • C. Schöber
    • 1
  • H. Link
    • 1
  • M. Freund
    • 1
  • A. Hanauske
    • 1
  • H.-J. Meyer
    • 1
  • W. Achterrath
    • 1
  • H. Poliwoda
    • 1
  1. 1.Medical SchoolHannover University3 HannoverGermany

Personalised recommendations