Fluorodeoxyuridine with continuous leucovorin infusion. A phase II clinical trial in patients with metastatic colorectal cancer.

ABSTRACT

BACKGROUND: Chemotherapy of colon cancer has used the modulation of 5-fluorouracil (5-FU) by leucovorin; however, early studies indicate that leucovorin with fluorodeoxyuridine (FUDR) may be clinically superior. The authors report their experience in patients with metastatic colorectal cancer. METHODS: One hundred twelve evaluable patients with metastatic colorectal cancer were treated with leucovorin and FUDR. Leucovorin was given by continuous intravenous infusion at 500 mg/m2/day on days 1-6, and FUDR was given by intravenous push on days 2-6 at 300 p.m. daily, with doses ranging from 270-1350 mg/m2/day. RESULTS: This regimen was well tolerated with dose-limiting toxicity of diarrhea and stomatitis, while hematologic toxicity was minimal. At least one chemotherapy regimen had previously failed in 90 of 112 patients (80%). Twenty major responses greater than or equal to partial remission, lasting from 2-40+ months, were observed in this patient population for an overall response rate of 18%. Twelve of 22 previously untreated patients (55%) had major responses. Overall survival of previously untreated patients was 73% (14 of 19) and 50% (11 of 22) at 1 and 2 years, respectively. Of 66 patients who had received prior leucovorin-5-FU (LVFU) therapy with subsequent disease progression, 4 had major responses lasting 95, 241, 350, and 432 days, respectively. CONCLUSIONS: These data suggest that the modulation of FUDR by leucovorin may have clinical use. The recommended starting dose of FUDR is 800 mg/m2/day on days 2-6, with subsequent escalation each month in those patients who do not display stomatitis.