Intravenous Weekly High-Dose Infusion of 5-Fluorouracil and Folinic Acid in Pretreated Patients with Metastatic Colorectal Cancer

Abstract

<i>Background: </i>Effective second-line treatments of inoperable metastatic colorectal cancer are rare. Therefore, the efficacy and toxicity of weekly intravenous high-dose infusions of 5-fluoro-uracil (5-FU) and folinic acid (FA) in pretreated patients with metastatic colorectal cancer were evaluated. <i>Patients and Methods: </i>In 32 patients, 580 applications of an intravenous high-dose infusion of 5-FU/FA were administered. All patients had been pretreated. Thirty patients had received hepatic arterial (n = 8) or intravenous infusions (n = 22) of 5-FU/FA and 2 patients, hepatic arterial infusions of 5-fluorodeoxyuridine (FUdR). The high-dose chemotherapy regimen consisted of a weekly intravenous infusion of FA (500 mg/m²) over 1 h, immediately followed by a continuous intravenous infusion of 5-FU over 24 h. The starting dose of 5-FU was 2,400 mg/m². One course consisted of 12 weekly applications, interrupted by 1 week after 6 applications and by 4 weeks after 12 applications. <i>Results: </i>Diarrhea, nausea, and vomiting were the most frequent manifestations of toxicity. Two patients experienced WHO grade IV diarrhea, 15 patients experienced one episode of WHO grade III diarrhea. Hematological toxicity was never observed. Partial remission was observed in 11/32 patients (34%) and disease stabilization in 9/32 patients (28%), while the disease progressed in 12/32 patients (38%) under intravenous high-dose 5-FU with FA. The median overall survival was 22 months after start of first-line treatment and 12 months after initiation of 24-hour high-dose treatment. <i>Conclusion: </i>5-FU given as an intravenous 24-hour high-dose infusion with FA is well tolerated and produced a further response in progressive patients who were refractory to regional or conventional intravenous 5-FU/FA treatment. Therefore, we recommend that this treatment should be further studied in patients with metastatic colorectal cancer whose disease progressed under conventional pretreatment.