Low-dose oral fluorouracil with eniluracil as first-line chemotherapy against advanced breast cancer: a phase II study.

Abstract

PURPOSE:

Eniluracil (776C85) is an effective inactivator of dihydropyrimidine dehydrogenase that allows continuous low-dose oral fluorouracil (5-FU) to be given with predicable oral bioavailability. We have assessed this as first-line oral chemotherapy for patients with advanced/metastatic breast cancer.

PATIENTS AND METHODS:

Patients with histologically proven, locally advanced or metastatic breast cancer without previous chemotherapy for advanced disease were entered onto this open-label phase II study. Patients received oral 5-FU 1.0 mg/m(2) with eniluracil 10 mg/m(2), both given twice daily for the first 28 days of each 35-day cycle, continuing until disease progression or unmanageable toxicity.

RESULTS:

Thirty-three patients were entered, with a median age of 53 years. Sixteen partial responses were seen in twenty-nine assessable patients (55%; 95% confidence interval, 37% to 73%), including responses in four (40%) out of 10 patients who had received prior adjuvant 5-FU. Seven patients had stable disease for at least 3 months with symptom improvement. Median response duration was 14 months (range, 10 to 18+ months). Toxicity was low. There were only two episodes of drug-related grade 3 nonhematologic toxicity (diarrhea and infection), and only 6%, 3%, and 3% of patients developed granulocytopenia, thrombocytopenia, and neutropenic sepsis, respectively. Mild (grade 1/2) diarrhea occurred in 39% of patients, hand-foot syndrome in 15%, nausea in 27%, and mucositis in 18%. Toxicity-associated delay and dose reduction occurred in only 2% and 5% of courses, respectively.

CONCLUSION:

First-line treatment with the combination of oral 5-FU and eniluracil has high activity in patients with advanced breast cancer comparable with the most active conventional cytotoxic agents but with strikingly less toxicity.

• Authors: I E Smith, S R Johnston, M E O'Brien, T F Hickish, R H de Boer, A Norton, D T Cirkel, C M Barton
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 18 Issue 12 Pg. 2378-84 (Jun 2000) ISSN: 0732-183X [Print] United States
• PMID: 10856097 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Enzyme Inhibitors
• eniluracil
• Uracil
• Fluorouracil

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, pharmacokinetics)
• Biological Availability
• Breast Neoplasms (drug therapy, pathology)
• Drug Administration Schedule
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Female
• Fluorouracil (administration & dosage, adverse effects, pharmacokinetics)
• Humans
• Middle Aged
• Treatment Outcome
• Uracil (administration & dosage, analogs & derivatives, pharmacology)