The role of interferon-α as a modulator of fluorouracil and leucovorin

J. L. Grem, C. J. van Groeningen, A. A. Ismail, P. G. Johnston, H. R. Alexander, C. J. Allegra

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Several preclinical studies have demonstrated that interferon-α (IFN-α) may enhance the cytotoxicity of fluoropyrimidines in a greater-than-additive manner in a variety of human cancer cell lines. The underlying mechanism(s) have varied in different cancer cell lines, and include increased fluorouracil anabolism to fluorodeoxyuridine monophosphate, further inhibition of thymidylate synthase, stimulation of thymidine and uridine phosphorylase activities, greater DNA damage, and enhanced natural killer cell-mediated lysis of tumour targets. These preclinical studies stimulated clinical evaluation of IFN-α in combination with 5-fluorouracil (5-FU) with and without leucovorin (LV), and the initial clinical results appeared promising. We summarise preclinical research concerning the interaction of 5-FU and IFN-α. The rationale for combining 5-FU with IFN-a and LV is discussed, and we describe our clinical experience with the combination of 5-FU, LV and IFN-α-2a. The insights and unresolved questions concerning the clinical application of this combination are also discussed.

Original languageEnglish (US)
Pages (from-to)1316-1320
Number of pages5
JournalEuropean Journal of Cancer
Volume31
Issue number7-8
DOIs
StatePublished - Jan 1 1995

Fingerprint

Leucovorin
Fluorouracil
Interferons
Uridine Phosphorylase
Floxuridine
Thymidine Phosphorylase
Cell Line
Thymidylate Synthase
Neoplasms
Natural Killer Cells
DNA Damage
Research

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Grem, J. L., van Groeningen, C. J., Ismail, A. A., Johnston, P. G., Alexander, H. R., & Allegra, C. J. (1995). The role of interferon-α as a modulator of fluorouracil and leucovorin. European Journal of Cancer, 31(7-8), 1316-1320. https://doi.org/10.1016/0959-8049(95)91267-G

The role of interferon-α as a modulator of fluorouracil and leucovorin. / Grem, J. L.; van Groeningen, C. J.; Ismail, A. A.; Johnston, P. G.; Alexander, H. R.; Allegra, C. J.

In: European Journal of Cancer, Vol. 31, No. 7-8, 01.01.1995, p. 1316-1320.

Research output: Contribution to journalArticle

Grem, JL, van Groeningen, CJ, Ismail, AA, Johnston, PG, Alexander, HR & Allegra, CJ 1995, 'The role of interferon-α as a modulator of fluorouracil and leucovorin', European Journal of Cancer, vol. 31, no. 7-8, pp. 1316-1320. https://doi.org/10.1016/0959-8049(95)91267-G
Grem JL, van Groeningen CJ, Ismail AA, Johnston PG, Alexander HR, Allegra CJ. The role of interferon-α as a modulator of fluorouracil and leucovorin. European Journal of Cancer. 1995 Jan 1;31(7-8):1316-1320. https://doi.org/10.1016/0959-8049(95)91267-G
Grem, J. L. ; van Groeningen, C. J. ; Ismail, A. A. ; Johnston, P. G. ; Alexander, H. R. ; Allegra, C. J. / The role of interferon-α as a modulator of fluorouracil and leucovorin. In: European Journal of Cancer. 1995 ; Vol. 31, No. 7-8. pp. 1316-1320.
@article{864f050da12a462dbde7ae48c6fd15cd,
title = "The role of interferon-α as a modulator of fluorouracil and leucovorin",
abstract = "Several preclinical studies have demonstrated that interferon-α (IFN-α) may enhance the cytotoxicity of fluoropyrimidines in a greater-than-additive manner in a variety of human cancer cell lines. The underlying mechanism(s) have varied in different cancer cell lines, and include increased fluorouracil anabolism to fluorodeoxyuridine monophosphate, further inhibition of thymidylate synthase, stimulation of thymidine and uridine phosphorylase activities, greater DNA damage, and enhanced natural killer cell-mediated lysis of tumour targets. These preclinical studies stimulated clinical evaluation of IFN-α in combination with 5-fluorouracil (5-FU) with and without leucovorin (LV), and the initial clinical results appeared promising. We summarise preclinical research concerning the interaction of 5-FU and IFN-α. The rationale for combining 5-FU with IFN-a and LV is discussed, and we describe our clinical experience with the combination of 5-FU, LV and IFN-α-2a. The insights and unresolved questions concerning the clinical application of this combination are also discussed.",
author = "Grem, {J. L.} and {van Groeningen}, {C. J.} and Ismail, {A. A.} and Johnston, {P. G.} and Alexander, {H. R.} and Allegra, {C. J.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1016/0959-8049(95)91267-G",
language = "English (US)",
volume = "31",
pages = "1316--1320",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "7-8",

}

TY - JOUR

T1 - The role of interferon-α as a modulator of fluorouracil and leucovorin

AU - Grem, J. L.

AU - van Groeningen, C. J.

AU - Ismail, A. A.

AU - Johnston, P. G.

AU - Alexander, H. R.

AU - Allegra, C. J.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Several preclinical studies have demonstrated that interferon-α (IFN-α) may enhance the cytotoxicity of fluoropyrimidines in a greater-than-additive manner in a variety of human cancer cell lines. The underlying mechanism(s) have varied in different cancer cell lines, and include increased fluorouracil anabolism to fluorodeoxyuridine monophosphate, further inhibition of thymidylate synthase, stimulation of thymidine and uridine phosphorylase activities, greater DNA damage, and enhanced natural killer cell-mediated lysis of tumour targets. These preclinical studies stimulated clinical evaluation of IFN-α in combination with 5-fluorouracil (5-FU) with and without leucovorin (LV), and the initial clinical results appeared promising. We summarise preclinical research concerning the interaction of 5-FU and IFN-α. The rationale for combining 5-FU with IFN-a and LV is discussed, and we describe our clinical experience with the combination of 5-FU, LV and IFN-α-2a. The insights and unresolved questions concerning the clinical application of this combination are also discussed.

AB - Several preclinical studies have demonstrated that interferon-α (IFN-α) may enhance the cytotoxicity of fluoropyrimidines in a greater-than-additive manner in a variety of human cancer cell lines. The underlying mechanism(s) have varied in different cancer cell lines, and include increased fluorouracil anabolism to fluorodeoxyuridine monophosphate, further inhibition of thymidylate synthase, stimulation of thymidine and uridine phosphorylase activities, greater DNA damage, and enhanced natural killer cell-mediated lysis of tumour targets. These preclinical studies stimulated clinical evaluation of IFN-α in combination with 5-fluorouracil (5-FU) with and without leucovorin (LV), and the initial clinical results appeared promising. We summarise preclinical research concerning the interaction of 5-FU and IFN-α. The rationale for combining 5-FU with IFN-a and LV is discussed, and we describe our clinical experience with the combination of 5-FU, LV and IFN-α-2a. The insights and unresolved questions concerning the clinical application of this combination are also discussed.

UR - http://www.scopus.com/inward/record.url?scp=0029093720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029093720&partnerID=8YFLogxK

U2 - 10.1016/0959-8049(95)91267-G

DO - 10.1016/0959-8049(95)91267-G

M3 - Article

C2 - 7577043

AN - SCOPUS:0029093720

VL - 31

SP - 1316

EP - 1320

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 7-8

ER -