Sequential methotrexate, 5‐fluorouracil (5‐FU), and high dose leucovorin versus 5‐FU and high dose leucovorin versus 5‐FU alone for advanced colorectal cancer. A multi‐institutional randomized trial

Background. The primary objective of this study was to compare the single‐biochemical modulation of 5‐fluo‐rouracil (5‐FU) and leucovorin with that of the double‐biochemical modulation of methotrexate and leucovorin. Because of the Martin et al. study in which an experimental model showed similar effects of 5‐FU at maximum tolerated doses to the modulation with leucovorin at standard doses, a third treatment arm of 5‐FU alone was also studied.

[1]  B. Glimelius.  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. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group. , 1993, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  R. Herrmann,et al.  Sequential methotrexate and 5-fluorouracil (FU) vs. FU alone in metastatic colorectal cancer. Results of a randomized multicenter trial. The Association of Medical Oncology (AIO) of the German Cancer Society. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  R. Herrmann,et al.  Original article: Sequential methotrexate and 5-fluorouracil (FU) vs. FU alone in metastatic colorectal cancer Results of a randomized multicenter trial , 1992 .

[4]  C. Boni,et al.  Fluorouracil-alone versus high-dose folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research (GOIRC). , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  J. Carles,et al.  Sequential Combination of Methotrexate (MTX), 5‐Fluorouracil (FU), and High‐Dose Folinic Acid (FA) in Advanced Colorectal Cancer: Double Biochemical Modulation? , 1991, American journal of clinical oncology.

[6]  S. Barni,et al.  Folinic acid + 5-fluorouracil (5-FU) versus equidose 5-FU in advanced colorectal cancer. Phase III study of 'GISCAD' (Italian Group for the Study of Digestive Tract Cancer). , 1991, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  J. Bertino,et al.  The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  J. Doroshow,et al.  Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  J. Laurie,et al.  Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  S. Arbuck,et al.  Overview of clinical trials using 5‐fluorouracil and leucovorin for the treatment of colorectal cancer , 1989, Cancer.

[11]  D. Martin,et al.  Failure of high-dose leucovorin to improve therapy with the maximally tolerated dose of 5-fluorouracil: a murine study with clinical relevance? , 1988, Journal of the National Cancer Institute.

[12]  C. Erlichman,et al.  A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  J. Bertino,et al.  Sequential methotrexate and 5-fluorouracil: mechanisms of synergy. , 1983, Seminars in oncology.

[14]  R. Heimer,et al.  Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism. , 1979, Science.

[15]  P. Piedbois.  Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  N. Petrelli,et al.  Comparison of unique leucovorin and 5-fluorouracil "escalating" and "maximum" dosage strategies. , 1987, NCI monographs : a publication of the National Cancer Institute.

[17]  N. Petrelli,et al.  Biochemical and pharmacologic basis for potentiation of 5-fluorouracil action by leucovorin. , 1987, NCI monographs : a publication of the National Cancer Institute.

[18]  B. Leone,et al.  Sequential therapy with methotrexate and 5-fluorouracil in the treatment of advanced colorectal carcinoma. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  A. Miller,et al.  Reporting results of cancer treatment , 1981, Cancer.

[20]  J. Bertino,et al.  Schedule-dependent antitumor effects of methotrexate and 5-fluorouracil. , 1977, Cancer research.