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Background. UFT is a fixed-ratio combination of uracil and Ftorafur, a prodrug that is absorbed orally and metabolized in vivo to 5-fluorouracil (5-FU). Uracil potentiates 5-FU through interference with its catabolism. The combination of UFT and leucovorin in patients with advanced incurable colorectal cancer, to evaluate preliminary activity and toxicity in this patient population. Methods. Twenty-one patients were treated. Twenty patients were evaluable for toxicity and response. Patients received UFT 350 mg/m2/day divided every 8 hours. Patients took a 5 mg tablet of leucovorin every 8 hours, concurrent with each UFT dose. Treatment was continued for 28 consecutive days, followed by a 7-day rest. Results. Five major objective responses (one complete and four partial) were observed. Toxicity was mild, with no dose-limiting myelosuppression. Four patients experienced grade 3 diarrhea or higher, and two patients experienced dose-limiting mucositis. Conclusion. UFT and low dose leucovorin is a well tolerated, orally administered regimen with activity in colorectal cancer. A randomized comparison of this regimen with conventional parenteral regimens is warranted.

Background: Biochemical modulation of bolus fluorouracil (5-FU) by addition of leucovorin to the treatment regimen has increased response in patients with disseminated colorectal cancer from fewer than 20% to more than 40%. In view of the short half-life of 5-FU and its cell cycle specificity, it may be that infusion rather than intravenous bolus injection would increase efficacy. Furthermore, the advent of safer indwelling intravenous catheters and pump technology, allowing home and ambulatory treatment, has made protracted infusion clinically feasible. To examine these questions, we conducted a phase I trial using protracted infusion of 5-FU by indwelling catheter and pump, with leucovorin given by bolus injection, and reported 40% partial response. Purpose: We have now initiated a phase II study of 5-FU given by prolonged continuous infusion with weekly bolus injections of leucovorin in previously untreated patients with measurable, disseminated colorectal cancer. Methods: Forty-one patients were treated. The regimen consisted of treatment for 4 weeks with 5-FU at a dose of 200 mg/[m.sup.2] daily as a continuous infusion by indwelling intravenous catheter and pump, followed by a 2-week rest and then by monthly cycles of 3 weeks of treatment and 1-week rest until disease progression. Leucovorin was given as a bolus injection of 20 mg/[m.sup.2] at the beginning of each week of treatment with 5-FU. Results: Nineteen (46%) of 41 patients had objective response: Three complete responses and 16 partial responses were seen. Overall, the median duration of response was 8 months. The median duration of survival was 16 months: 18 months for responders and 10 months for nonresponders. In general, toxic effects were mild and consisted primarily of stomatitis and palmarplantar erythrodysesthesia (hand-foot syndrome). Neither grade 4 toxic effects nor treatment-related deaths were observed. The only serious side effects were catheter thrombosis (three patients) and catheter sepsis (one patient). Conclusion: We conclude that this safe regimen is one of the most effective for the treatment of disseminated colorectal cancer. Implications: The regimen should be tested prospectively against other regimens in use for this disease. It is currently included in a phase III study of the Southwest Oncology Group for this purpose. That study will assess quality of life as well as response rates and survival duration. [J Natl Cancer Inst 85:41-44, 1993]

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• The most common metabolic complications of total parenteral nutrition (TPN), glucose intolerance and abnormal liver function, can be significantly reduced when 30% of the glucose calories are replaced by fat. We gave 88 patients either conventional TPN (CON-TPN, 25% dextrose and 4.25% amino acids) or modified TPN (MOD-TPN, 15% dextrose, fat, and 5% amino acids). The treatment groups were as follows: group A, no surgery with TPN only; group B, postoperative TPN; and group C, preoperative and postoperative TPN. Serial blood samples were analyzed for glucose, albumin, triglycerides, and insulin, and for liver function values. Nine patients manifested hyperglycemia and were removed from the study; seven patients had received CON-TPN and two had received MOD-TPN. In group A, the insulin level rose 50% less with MOD-TPN. There was a 50% smaller rise in the triglyceride, SGOT, and SGPT levels in patients who received MOD-TPN. Replacing one third of the TPN glucose calories with fat leads to better glucose tolerance and fewer hepatic complications.(Arch Surg 1984;119:1294-1298)