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 language | English (US) |
|---|---|
| Pages (from-to) | 1576-1582 |
| Number of pages | 7 |
| Journal | Annals of Oncology |
| Volume | 13 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2002 |
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Keywords
- 5-Fluorouracil
- Clinical trial
- Eniluracil
- Oral chemotherapy
- Pancreatic cancer
- Phase II
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
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.
PY - 2002/10/1
Y1 - 2002/10/1
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.
AB - 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.
KW - 5-Fluorouracil
KW - Clinical trial
KW - Eniluracil
KW - Oral chemotherapy
KW - Pancreatic cancer
KW - Phase II
UR - http://www.scopus.com/inward/record.url?scp=0036809020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036809020&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdf274
DO - 10.1093/annonc/mdf274
M3 - Article
C2 - 12377645
AN - SCOPUS:0036809020
VL - 13
SP - 1576
EP - 1582
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 10
ER -