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Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer.
Abstract
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 low-dose leucovorin has now been shown to offer a statistically significant survival advantage versus 5FU alone and versus 5FU plus high-dose MTX, a regimen that had shown promise in earlier trials. These data confirm the efficacy of leucovorin combined with 5FU in patients with advanced colorectal cancer and establish that it is not necessary to use high doses of leucovorin to achieve these results.
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Citations
Cited by
Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): A review
Malet-Martino, M., & Martino, R. (2002) · The Oncologist · doi:10.1634/theoncologist.7-4-288 · Cited by 382
Leichman, C. G., Fleming, T. R., Muggia, F. M., Tangen, C. M., Ardalan, B., Doroshow, J. H., Meyers, F. J., Holcombe, R. F., Weiss, G. R., & Mangalik, A. (1995) · Journal of Clinical Oncology · doi:10.1200/jco.1995.13.6.1303 · Cited by 359
Gamelin, E., Delva, R., Jacob, J., Merrouche, Y., Raoul, J. L., Pezet, D., Dorval, E., Piot, G., Morel, A., & Boisdron-Celle, M. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.3934 · Cited by 346
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Peters, G. J., van der Wilt, C. L., van Moorsel, C. J. A., Kroep, J. R., Bergman, A. M., & Ackland, S. P. (2000) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(00)00086-3 · Cited by 301
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Metadata
- Authors
- Poon, M. A., O'Connell, M. J., Wieand, H. S., Krook, J. E., Gerstner, J. B., Tschetter, L. K., Levitt, R., Kardinal, C. G., & Mailliard, J. A.
- Venue
- Journal of Clinical Oncology
- Published
- 1991-11
- Volume
- 9
- Issue
- 11
- Pages
- 1967-1972
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W1844072307
- Cited by
- 375
- References
- 0
- FWCI
- 8.71
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. https://app.cochat.ai/papers/10.1200/jco.1991.9.11.1967
- The paper
- Poon, M. A., O'Connell, M. J., Wieand, H. S., Krook, J. E., Gerstner, J. B., Tschetter, L. K., Levitt, R., Kardinal, C. G., & Mailliard, J. A. (1991). Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. Journal of Clinical Oncology. https://doi.org/10.1200/jco.1991.9.11.1967
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
