A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon

Brian G. Czito, Timothy J. Hong, Darrel P. Cohen, Douglas Tyler, Catherine G. Lee, Mitchell S. Anscher, Kirk A. Ludwig, Hilliard F. Seigler, Christopher Mantyh, Michael A. Morse, Albert C. Lockhart, William P. Petros, Wanda Honeycutt, Neil L. Spector, Phillip J. Ertel, Steve G. Mangum, Herbert I. Hurwitz

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Purpose: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase, allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU combined with preoperative radiotherapy and determined the recommended Phase II dose and dose-limiting toxicity in patients with locally advanced rectal and colon cancer. Methods and Materials: Patients with TNM Stage II or III rectal cancer and residual or recurrent colon cancer received eniluracil (starting at 6.0 mg/m2 every 12 h) and 5-FU (starting at 0.6 mg/m2 every 12 h). Eniluracil and 5-FU were given with a 5-week course of preoperative radiotherapy of 4500 cGy, with a possible 540-cGy boost. Surgery was performed approximately 4 weeks after completion of chemoradiotherapy. Results: Twenty-two patients were enrolled; 1 patient was withdrawn owing to noncompliance. Chemotherapy was completed in all patients; radiotherapy was completed in 20 patients. The recommended Phase II dose of eniluracil and 5-FU was 8 mg/m2 every 12 h and 0.8 mg/m2 every 12 h, respectively. Diarrhea was the dose-limiting toxicity. Eleven of the 17 patients with primary rectal cancer underwent a sphincter-sparing procedure. One patient had a pathologic complete response. Conclusion: Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well tolerated. Additional investigation is warranted.

Original languageEnglish (US)
Pages (from-to)779-785
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume58
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

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Keywords

  • 5-Fluorouracil
  • Colorectal cancer
  • Eniluracil
  • Phase I
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Czito, B. G., Hong, T. J., Cohen, D. P., Tyler, D., Lee, C. G., Anscher, M. S., Ludwig, K. A., Seigler, H. F., Mantyh, C., Morse, M. A., Lockhart, A. C., Petros, W. P., Honeycutt, W., Spector, N. L., Ertel, P. J., Mangum, S. G., & Hurwitz, H. I. (2004). A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon. International Journal of Radiation Oncology Biology Physics, 58(3), 779-785. https://doi.org/10.1016/S0360-3016(03)01567-0