A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon α -2a in adenocarcinoma of the large bowel

  • Authors:
    • Abdel Salam Attia Ismail
    • Mary G. Quinn
    • Maurice A. Wright
    • Aaron Ernst
    • Vivian Kao
    • Liam Grogan
    • Allison Parr
    • Frank Grollman
    • Ilan R. Kirsch
    • Jean L. Grem
  • View Affiliations

  • Published online on: June 1, 2005     https://doi.org/10.3892/or.13.6.1145
  • Pages: 1145-1152
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Abstract

We have reported that increasing the length of infusion from 5 min to 1 h appeared to substantially reduce the toxicity associated with fluorouracil (5-FU) modulated by leucovorin (LV) and interferon α-2a (IFN-α). This phase II study assessed the antitumor efficacy of this regimen. Patients (n=38) with colorectal cancer received IFN-α 5 MU/m2 SC on days 1-6; on days 2-6, LV 200 mg/m2 IV was given with 5-FU at initial doses of 370-425 mg/m2/h. The regimen was well-tolerated with no grade 4 toxicity. At 425 mg/m2 5-FU, grade 3 toxicities included diarrhea (8.6%), anorexia, fever and fatigue (5.7% each), neutropenia and nausea/vomiting (2.9% each). Individuals tolerated 5-FU doses up to 644 mg/m2. Objective responses occurred in 27% of 37 patients; median time to progression and survival were 6.1 and 12.9 months. Only 1 of 25 informative tumor samples had high-frequency microsatellite instability (MSI), while 7 of 23 assessable patients (30%) with MSI-negative tumors had an objective response. With 425 mg/m2, the average 5-FU Cp and AUC0-1 h were 37.4 µM and 1161 µM/h. Some 6 patients had extended sampling, and the half-lives of 5-FU and FBAL (apparent) were 8.6 and 100.0 min, respectively. A 1-h infusion of 5-FU is well tolerated; individual dose escalation of 5-FU allows each patient to receive the maximum tolerable dose.

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June 2005
Volume 13 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ismail AS, Quinn MG, Wright MA, Ernst A, Kao V, Grogan L, Parr A, Grollman F, Kirsch IR, Grem JL, Grem JL, et al: A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon α -2a in adenocarcinoma of the large bowel. Oncol Rep 13: 1145-1152, 2005
APA
Ismail, A.S., Quinn, M.G., Wright, M.A., Ernst, A., Kao, V., Grogan, L. ... Grem, J.L. (2005). A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon α -2a in adenocarcinoma of the large bowel. Oncology Reports, 13, 1145-1152. https://doi.org/10.3892/or.13.6.1145
MLA
Ismail, A. S., Quinn, M. G., Wright, M. A., Ernst, A., Kao, V., Grogan, L., Parr, A., Grollman, F., Kirsch, I. R., Grem, J. L."A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon α -2a in adenocarcinoma of the large bowel". Oncology Reports 13.6 (2005): 1145-1152.
Chicago
Ismail, A. S., Quinn, M. G., Wright, M. A., Ernst, A., Kao, V., Grogan, L., Parr, A., Grollman, F., Kirsch, I. R., Grem, J. L."A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon α -2a in adenocarcinoma of the large bowel". Oncology Reports 13, no. 6 (2005): 1145-1152. https://doi.org/10.3892/or.13.6.1145