Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer.

作者：Michael A. Poon, Michael J. O'Connell, Harry S. Wieand, James Edward Krook, James B. Gerstner, Loren K. Tschetter, Ralph Levitt, Carl G. Kardinal, James A. Mailliard · 发表于：Journal of Clinical Oncology · 年份：1991 · DOI：10.1200/jco.1991.9.11.1967 · 被引用次数：377 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Treatment and Pharmacology、Genetic factors in colorectal cancer

In a previous study (J Clin Oncol 7:1407-1417, 1989), we identified two dosage administration schedules of fluorouracil (5FU) combined with leucovorin that were superior to single-agent 5FU for the treatment of advanced colorectal cancer. In this same study, a regimen of 5FU plus high-dose methotrexate (MTX) demonstrated a suggestive advantage over 5FU alone. To permit a more definitive comparison, we have extended our evaluation of these three regimens to involve an additional 259 patients. In all, 457 patients with advanced colorectal cancer were randomly assigned to one of the following regimens: 5FU plus low-dose leucovorin, 5FU plus high-dose leucovorin, or 5FU plus high-dose MTX with leucovorin rescue. We have found that each of the 5FU/leucovorin regimens demonstrates a significant (P less than or equal to .01) advantage over 5FU plus high-dose MTX for objective tumor response and interval to tumor progression. Moreover, 5FU plus low-dose leucovorin confers a significant survival benefit (P less than or equal to .01) compared with 5FU plus high-dose MTX. The 5FU plus high-dose leucovorin regimen shows a survival benefit only in unadjusted analyses (P = .04), but this difference is not significant when adjusted for imbalances in prognostic variables (P = .44). Evaluation of the two 5FU/leucovorin regimens rules out a 10% decrease in death rate for the high-dose leucovorin regimen compared with the low-dose leucovorin regimen (P less than .05). The regimen of 5FU plus lo...