PHASE-II TRIAL OF 5-FLUOROURACIL AND HIGH-DOSE FOLINIC ACID AS 1ST-LINE OR 2ND-LINE THERAPY FOR ADVANCED BREAST-CANCER

The use of leucovorin to modulate 5-fluorouracil (FUra)-mediated inhib ition of thymidylate synthase has been shown both in vitro and in vivo to improve the antitumor activity of FUra. Based on the activity of t his combination in previously untreated patients, we performed a study of FUra and high-dose leucovorin (HDFA) in patients with metastatic b reast cancer and minimal prior chemotherapy. Patients were stratified by prior chemotherapy (or relapse within 12 months of completing adjuv ant chemotherapy) versus no prior chemotherapy (or relapse at greater than 12 months since completion of adjuvant chemotherapy). FUra was gi ven daily for 5 days at 370 mg/m2/day with HDFA, 500 mg/m2/day, beginn ing 24 hours before and continuing 12 hours beyond the first and last FUra doses, respectively. Two objective responses occurred among 21 pa tients in the pretreated group (10%; 95% confidence interval: 1-30%). Four of 36 eligible patients (11%) in the ''no prior therapy group'' h ad complete responses (95% confidence interval: 3-26%). The major toxi cities were moderate leucopenia and mucositis. We conclude that FUra p lus leucovorin has modest antitumor activity in metastatic breast canc er.