A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract

Brian G. Czito, Timothy J. Hong, Darrel P. Cohen, William P. Petros, Douglas S. Tyler, Theodore N. Pappas, Daohai Yu, Catherine G. Lee, Albert Lockhart, Michael A. Morse, Nishan Fernando, Herbert I. Hurwitz

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. Methods and Materials: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m2 q12h)/5-FU (starting at 0.6 mg/m2 q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. Results: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m2 q12h/1 mg/m2 q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. Conclusion: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalCancer Investigation
Volume24
Issue number1
DOIs
StatePublished - Feb 22 2006
Externally publishedYes

Fingerprint

Biliary Tract
Pancreatic Neoplasms
Fluorouracil
Radiotherapy
Dihydrouracil Dehydrogenase (NADP)
Biliary Tract Neoplasms
eniluracil
Cholangiocarcinoma
Chemoradiotherapy
Neoplasms
Radiation
Morbidity
Safety

Keywords

  • 5-Fluorouracil
  • Eniluracil
  • Pancreatic cancer
  • Phase I
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract. / Czito, Brian G.; Hong, Timothy J.; Cohen, Darrel P.; Petros, William P.; Tyler, Douglas S.; Pappas, Theodore N.; Yu, Daohai; Lee, Catherine G.; Lockhart, Albert; Morse, Michael A.; Fernando, Nishan; Hurwitz, Herbert I.

In: Cancer Investigation, Vol. 24, No. 1, 22.02.2006, p. 9-17.

Research output: Contribution to journalArticle

Czito, Brian G. ; Hong, Timothy J. ; Cohen, Darrel P. ; Petros, William P. ; Tyler, Douglas S. ; Pappas, Theodore N. ; Yu, Daohai ; Lee, Catherine G. ; Lockhart, Albert ; Morse, Michael A. ; Fernando, Nishan ; Hurwitz, Herbert I. / A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract. In: Cancer Investigation. 2006 ; Vol. 24, No. 1. pp. 9-17.
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abstract = "Purpose: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. Methods and Materials: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m2 q12h)/5-FU (starting at 0.6 mg/m2 q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. Results: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m2 q12h/1 mg/m2 q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. Conclusion: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.",
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T1 - A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract

AU - Czito, Brian G.

AU - Hong, Timothy J.

AU - Cohen, Darrel P.

AU - Petros, William P.

AU - Tyler, Douglas S.

AU - Pappas, Theodore N.

AU - Yu, Daohai

AU - Lee, Catherine G.

AU - Lockhart, Albert

AU - Morse, Michael A.

AU - Fernando, Nishan

AU - Hurwitz, Herbert I.

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N2 - Purpose: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. Methods and Materials: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m2 q12h)/5-FU (starting at 0.6 mg/m2 q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. Results: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m2 q12h/1 mg/m2 q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. Conclusion: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.

AB - Purpose: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. Methods and Materials: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m2 q12h)/5-FU (starting at 0.6 mg/m2 q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. Results: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m2 q12h/1 mg/m2 q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. Conclusion: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.

KW - 5-Fluorouracil

KW - Eniluracil

KW - Pancreatic cancer

KW - Phase I

KW - Radiation

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