Faculty Collaboration Database

A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon. Int J Radiat Oncol Biol Phys 2004 Mar 01;58(3):779-85

Date

02/18/2004

Pubmed ID

14967434

DOI

10.1016/S0360-3016(03)01567-0

Scopus ID

2-s2.0-10744222901 (requires institutional sign-in at Scopus site)   7 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/m(2) every 12 h) and 5-FU (starting at 0.6 mg/m(2) 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RESULTS: Twenty-two patients were enrolled; 1 patient was withdrawn owing to noncompliance.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/m(2) every 12 h and 0.8 mg/m(2) 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.

Author List

Czito BG, Hong TJ, Cohen DP, Tyler DS, Lee CG, Anscher MS, Ludwig KA, Seigler HF, Mantyh C, Morse MA, Lockhart AC, Petros WP, Honeycutt W, Spector NL, Ertel PJ, Mangum SG, Hurwitz HI

Author

Kirk A. Ludwig MD Chief, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Administration, Oral
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic
Colonic Neoplasms
Combined Modality Therapy
Drug Combinations
Enzyme Inhibitors
Female
Fluorouracil
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Rectal Neoplasms
Uracil