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

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

Research output: Contribution to journalArticle

4 Scopus citations

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 AUC 0-1 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.

Original languageEnglish (US)
Pages (from-to)1145-1152
Number of pages8
JournalOncology reports
Volume13
Issue number6
DOIs
StatePublished - Jun 2005

Keywords

  • Adenocarcinoma
  • Fluorouracil
  • Interferon α-2a
  • Large bowel
  • Leucovorin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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