A phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma.

Abstract

Twenty-two patients with advanced colorectal carcinoma were enrolled in this study. Ten patients had received prior chemotherapy that included the combination of fluorouracil (5-FU) and leucovorin (LV). All patients required subcutaneous port insertion and portable external infusion pumps to allow outpatient treatment. 5-FU (2,600 mg/m2) was administered concurrently with LV (500 mg/m2) over 24 hours of continuous infusion. The mean steady-state plasma concentration of 5-FU was 10 mumol/L (range, 7 to 14 mumol/L). The 5-FU dose was based on our previous phase I study, in which maximum-tolerated dose (MTD) of 5-FU was determined to be 2,600 mg/m2 in combination with a fixed dose of LV at 500 mg/m2. The treatment was repeated weekly. Twenty-two patients received a total of 560 courses of treatment. Eleven instances of grade 2-3 toxicity were observed: diarrhea (five), stomatitis (three), hand/foot syndrome (three). The overall objective response was 45% (10 of 22) and among previously untreated patients was 58%. Three of the responders achieved complete response (CR), with lung and liver as the metastatic sites. The median duration of survival for the previously untreated patients was not reached at 22 months, and was 10 months for the previously treated patients. These results suggest that short-term infusional therapy of 5-FU and LV in patients with advanced metastatic colorectal cancer generates acceptable toxicity, with equivalent or superior survivability in previously treated and untreated patients versus alternative methods of administration of the two agents.

A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer

“…In the study presented here as well as in our previous study, 5-FU was administered as a protracted, weekly 24 h infusion combined with folinic acid, since this mode of application appears to be less toxic and potentially more active as compared to the bolus administration. This regimen was initially investigated in patients with colon cancer and showed a good activity with low toxicity (Ardalan et al, 1991). In gastric cancer, one study had reported the use of protracted 24 h continuous infusion of high-dose 5-FU achieving a remission rate of 24% and a stable disease rate of 59% in patients previously treated with bolus 5-FU therapy .…”

P53 overexpression predicts poor chemosensitivity to high‐dose 5‐fluorouracil plus leucovorin chemotherapy for stage IV colorectal cancers after palliative bowel resection

“…However, one may argue that the impact of our study was reduced because the allocation of patients into treatment arms was not randomized. 48 Actually, because high-dose 5-fluorouracil plus leucovorin chemotherapy was generally accepted as the mainstay treatment for patients with metastatic colorectal cancers, 50,52 randomization of patients was thus ethically impossible in our clinical setting. Nevertheless, in our study, all the patients assigned to either treatment arm were based on the same eligibility criteria.…”

5-Flourouracil–Induced Encephalopathy in Parkinson’s disease

“…1 The incidence of encephalopathy with high dose infusional 5-FU can be as high as 5.7%. 2 In general, neurotoxicity frequency is between 0.9-7 percent.…”