Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: A Southwest Oncology Group study

M. L. Rothenberg, J. K. Benedetti, J. S. Macdonald, T. E. Seay, M. A. Neubauer, C. S. George, Michael Tanaka, J. K. Giguere, B. T. Pruitt, J. L. Abbruzzese

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Abstract

Background: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. Patients and Methods: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m2 /day p.o. on days 2-6 of a 28-day treatment cycle. Results: In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment. Conclusions: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.

Original languageEnglish (US)
Pages (from-to)1576-1582
Number of pages7
JournalAnnals of Oncology
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2002

Fingerprint

Pancreatic Neoplasms
Fluorouracil
Drug Therapy
Survival
Survival Rate
Dihydrouracil Dehydrogenase (NADP)
eniluracil
Confidence Intervals
Neutropenia
Biological Availability
Half-Life
Pancreas
Diarrhea
Adenocarcinoma
Therapeutics
Enzymes

Keywords

  • 5-Fluorouracil
  • Clinical trial
  • Eniluracil
  • Oral chemotherapy
  • Pancreatic cancer
  • Phase II

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rothenberg, M. L., Benedetti, J. K., Macdonald, J. S., Seay, T. E., Neubauer, M. A., George, C. S., ... Abbruzzese, J. L. (2002). Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: A Southwest Oncology Group study. Annals of Oncology, 13(10), 1576-1582. https://doi.org/10.1093/annonc/mdf274

Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer : A Southwest Oncology Group study. / Rothenberg, M. L.; Benedetti, J. K.; Macdonald, J. S.; Seay, T. E.; Neubauer, M. A.; George, C. S.; Tanaka, Michael; Giguere, J. K.; Pruitt, B. T.; Abbruzzese, J. L.

In: Annals of Oncology, Vol. 13, No. 10, 01.10.2002, p. 1576-1582.

Research output: Contribution to journalArticle

Rothenberg, ML, Benedetti, JK, Macdonald, JS, Seay, TE, Neubauer, MA, George, CS, Tanaka, M, Giguere, JK, Pruitt, BT & Abbruzzese, JL 2002, 'Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: A Southwest Oncology Group study', Annals of Oncology, vol. 13, no. 10, pp. 1576-1582. https://doi.org/10.1093/annonc/mdf274
Rothenberg, M. L. ; Benedetti, J. K. ; Macdonald, J. S. ; Seay, T. E. ; Neubauer, M. A. ; George, C. S. ; Tanaka, Michael ; Giguere, J. K. ; Pruitt, B. T. ; Abbruzzese, J. L. / Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer : A Southwest Oncology Group study. In: Annals of Oncology. 2002 ; Vol. 13, No. 10. pp. 1576-1582.
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abstract = "Background: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. Patients and Methods: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m2 /day p.o. on days 2-6 of a 28-day treatment cycle. Results: In 106 patients evaluable for survival, the 6-month survival rate was 34{\%} [95{\%} confidence interval (CI) 22{\%} to 47{\%}, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29{\%} (95{\%} CI 16{\%} to 42{\%}, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8{\%} and 2{\%}, respectively. The most common grade 3-4 toxicities were neutropenia (29{\%} of patients) and diarrhea (12{\%} of patients). Overall, 69{\%} of patients experienced a grade 3 or worse adverse event during treatment. Conclusions: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.",
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T1 - Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer

T2 - A Southwest Oncology Group study

AU - Rothenberg, M. L.

AU - Benedetti, J. K.

AU - Macdonald, J. S.

AU - Seay, T. E.

AU - Neubauer, M. A.

AU - George, C. S.

AU - Tanaka, Michael

AU - Giguere, J. K.

AU - Pruitt, B. T.

AU - Abbruzzese, J. L.

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N2 - Background: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. Patients and Methods: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m2 /day p.o. on days 2-6 of a 28-day treatment cycle. Results: In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment. Conclusions: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.

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