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Double Biochemical Modulation of 5-Fluorouracil by Methotrexate and Folinic Acid for the Treatment of Advanced Colorectal Cancer

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Abstract

Objective: We investigated the double biochemical modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and folinic acid (FA) for the treatment of 65 patients with advanced colorectal cancer. In particular, we studied the response and toxicity of the regimen.

Methods: A combination of MTX 130 mg/m2 intravenously at day 0, followed 24 hours later by FA orally as MTX rescue, and FA 300 mg/m2 intravenously daily (days 1 to 4) followed by 5-FU 500 mg/m2 intravenously daily (days 1 to 4) was administered.

Results: Objective response was achieved by 23 patients, with three complete and 20 partial responses [35%: 95% confidence interval (CI) 23 to 48%]. Median survival of the group was 12 months (range 6 to 36 months).

Conclusion: According to these results, double biochemical modulation of 5-FU with MTX and FA led to a significantly higher response rate followed by considerable toxicity.

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References

  1. Houghton A, Maroda SJ, Philips JO, et al. Biochemical determinants of responsiveness to 5 fluorouracil and its derivatives in xenografts of human colorectal adenocarcinoma in mice. Cancer Res 1981; 41: 144–9

    PubMed  CAS  Google Scholar 

  2. Poon MA, O’Connell MJ, Moertel CG, et al. Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol 1989; 7: 1407–18

    PubMed  CAS  Google Scholar 

  3. Einhorn LH. Improvements in fluorouracil chemotherapy? J Clin Oncol 1989; 10: 1377–9

    Google Scholar 

  4. Cadman E, Heimer R, Lavis L. Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism. Science 1979; 205: 1135–7

    Article  PubMed  CAS  Google Scholar 

  5. Benz C, Cadman E. Modulation of 5-fluorouracil metabolism and cytotocixity by antimetabolite pretreatment in human colorectal adenocarcinoma I-ICT-8. Cancer Res 1981; 41: 994–9

    PubMed  CAS  Google Scholar 

  6. Advanced Colorectal Cancer Metaanalysis Project Metaanalysis of randomised trials testing the biochemical modulation of 5-fluorouracil by methotrexate in metastatic colorectal cancer. J Clin Oncol 1994; 12: 960-9

    Google Scholar 

  7. Abad A Rosell R. Pastor MC, et al. Sequential combination of methotrexate (MTX) 5-fluorouracil (FU) and high dose folinic acid (FA) in advanced colorectal cander: double biochemical modulation? Am J Clin Oncol 1991; 14: 393–6

    Article  PubMed  CAS  Google Scholar 

  8. Polyzos A, Tsavaris N, Giannopoulos A, et al. Biochemical modulation of fluorouracil: comparison of methotrexate, folinic acid and fluorouracil versus folinic acid and fluorouracil in advanced colorectal cancer, a randomized trial. Cancer Chemother Pharmacol 1996; 38: 292–7

    Article  PubMed  CAS  Google Scholar 

  9. Romero A, Perez J, Cuevas M, et al. Double modulation of 5 fluorouracil by methotrexate and high dose L-Leucovorin in advanced colorectal cancer [abstract]. Proc Am Soc Clin Oncol 1995; 14: 209

    Google Scholar 

  10. Cornelia P, Palmieri G, Lorusso V, et al. Double biochemical modulation of 5. fluorouracil by methotrexate and Levofolinic acid in the treatment of advanced digestive tract malignancies. Eur J Cancer 1996; 32M 10: 1719–26

    Google Scholar 

  11. Miller AB, Hoogstraten B, Staquet M, et al. Reporting results of cancer treatment. Cancer 1981; 47: 207–14

    Article  PubMed  CAS  Google Scholar 

  12. Gralla R. Approaches to management of emesis. Clinician 1988; 6: 26–39

    Google Scholar 

  13. Kaplan EL, Meier P. Nonparametric estimation for incomplete observations. J Am Stat Assoc 1958; 53: 457–81

    Article  Google Scholar 

  14. Gehan EA. The determination of the number of patients required in a preliminaly and follow-up trial of a new chemotherapeutic agent. J Chronic Dis 1961; 2: 346–53

    Article  Google Scholar 

  15. Advanced Colorectal Cancer Metaanalysis Project. Modulation of fluorouracil by leukovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J Clin Oncol 1992; 10: 896–903

    Google Scholar 

  16. Herman R, Knuth A, Kleeberg O, et al. Sequential methotrexate and 5-fluorouracil vs 5-FU alone in metastatic colorectal cancer. Ann Oncol 1992; 3: 539–43

    Google Scholar 

  17. The Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Superiority of sequential methotrexate, fluorouracil, and leucovorin to fluorouracil alone in advanced symptomatic colorectal carcinoma: a randomized trial. J Clin Oncol 1989; 7: 1437–66

    Google Scholar 

  18. Marsh JC, Bertino JR, Katz KH, et al. The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer. J Clin Oncol 1991; 9: 371–80

    PubMed  CAS  Google Scholar 

  19. Glimelius B, Gimman C, Graffman S, et al. Sequential methotrexat -5FU-leucovorin (MFL) in advanced colorectal cancer. Eur J Clin Oncol 1986; 22: 295–300

    Article  CAS  Google Scholar 

  20. Cadman E, Heimer R, Benz C. The influence of methotrexate pretreatment of 5-fluorouracil metabolism in L1210 cells. J Biol Chem 1981; 256: 1695–704

    PubMed  CAS  Google Scholar 

  21. Glimelius B. Biochemical modulation of 5-fluorouracil: a randomized comparison of sequential methotrexate, 5-fluorouracil and leucovorin versus sequential 5-fluorouracil and leucovorin in patients with advanced symptomatic colorectal cancer. Ann Oncol 1993; 4: 235–40

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. 1st Department of Propedeutic Medicine, Athens University School of Medicine, Laikon Hospital Goudi, 11527, Athens, Greece

    A. Polyzos (Medical Oncologist, Assistant Professor of Medicine), N. Tsavaris, C. Kosmas, G. Petrikos, D. Stamatiadis, N. Kalahanis, A. Giannopoulos, G. Karatzas & P. P. Sfikakis

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  1. A. Polyzos
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  2. N. Tsavaris
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  3. C. Kosmas
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  4. G. Petrikos
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  5. D. Stamatiadis
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  6. N. Kalahanis
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  7. A. Giannopoulos
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  8. G. Karatzas
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  9. P. P. Sfikakis
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Polyzos, A., Tsavaris, N., Kosmas, C. et al. Double Biochemical Modulation of 5-Fluorouracil by Methotrexate and Folinic Acid for the Treatment of Advanced Colorectal Cancer. Clin. Drug Investig. 17, 83–88 (1999). https://doi.org/10.2165/00044011-199917020-00001

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  • DOI: https://doi.org/10.2165/00044011-199917020-00001

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