"Low-Dose Oral Fluorouracil With Eniluracil as First-Line Chemotherapy Against Advanced Breast Cancer: A Phase II Study".

Ian E. Smith, Stephen R. D. Johnston, Mary E. R. O’Brien, Tamas F. Hickish, Richard H. de Boer, Alison Norton, Deborah T. Cirkel, and Claire M. Barton.

From the Royal Marsden Hospital, Sutton and London; The Kent Cancer Centre, Maidstone; Royal Bournemouth Hospital, Bournemouth; and Glaxo Wellcome Research and Development, Middlesex, United Kingdom.

Address reprint requests to Ian E. Smith, MD, Department of Medicine, Royal Marsden Hospital, Fulham Road, London SW3 6JJ.

Abstract:
Purpose:
Patients and Methods:
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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/m² with eniluracil 10 mg/m², 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.

Additional Reference:

1. Allen BL, and Frenster JH, "Low-Dose Combination Chemotherapy of Disseminated Human Neoplasms".

2. Frenster JH, "Phase 2 Clinical Study of  Low-Dose Combination Chemotherapy of Unusual Human Neoplasms", Cancer Chemotherapy Reports, 57: 89 (February, 1973).