UFT Indication
UFT (tegafur and uracil) is indicated as an oral fluoropyrimidine alternative to intravenous 5-FU/leucovorin for the treatment of metastatic colorectal cancer, and has demonstrated efficacy in the adjuvant setting for resected stage I-III colorectal cancer, particularly in Asian populations. 1
Primary Indications
Metastatic Colorectal Cancer
- UFT plus oral leucovorin serves as an alternative to intravenous 5-FU/LV as monotherapy for first-line palliative chemotherapy in unresectable metastatic colorectal cancer. 1
- The experience and database with capecitabine is more extensive than with UFT in Western populations, making capecitabine the preferred oral fluoropyrimidine in most guidelines. 1
- UFT 300 mg/m²/day in three divided doses plus oral leucovorin 150 mg/day (50 mg three times daily) for 28 days every 5 weeks produces response rates of approximately 20-42% in advanced colorectal cancer. 2, 3
Adjuvant Therapy for Resected Colorectal Cancer
- UFT/leucovorin has shown benefit in the adjuvant setting after curative resection of colorectal liver metastases, particularly in patients with multiple metastases. 1
- A phase III trial demonstrated improved recurrence-free survival with UFT/LV versus surgery alone in the subgroup with multiple liver metastases (P=0.019). 1
- UFT has been shown to be equally effective with comparable toxicity when compared with bolus 5-FU/FA in patients both younger and older than 60 years. 1
Additional Cancer Indications
Non-Small Cell Lung Cancer (Stage IA)
- Japanese trials suggest UFT given continuously for up to 2 years may benefit patients with resected stage IA adenocarcinoma, though this remains controversial in Western practice. 1
- A pooled meta-analysis suggested benefit of UFT for patients with resected primarily adenocarcinoma, stage IA disease. 1
- However, the poor response rate (<10%) in advanced NSCLC raises questions about UFT's usefulness in the adjuvant setting, and adjuvant chemotherapy is generally not indicated for completely resected stage IA disease in Western guidelines. 1
Gastric Cancer
- UFT has shown activity as a single agent and in combination for advanced gastric cancer. 1
- UFT is listed among agents with demonstrated activity in advanced gastric cancer, though specific response rates and optimal combinations require further validation. 1
Dosing and Administration
Standard Regimen
- UFT 300 mg/m²/day (in three divided doses every 8 hours) plus oral leucovorin 90-150 mg/day for 28 days, followed by a 7-day rest period. 4, 2
- This dosing provides prolonged exposure to 5-FU with sustained plasma and tumor concentrations. 5, 2
Food Interaction - Critical Caveat
- UFT/leucovorin should NOT be administered with food; patients should avoid food for 1 hour before and after dosing. 4
- Food decreases CMAX and AUC of uracil and 5-FU by 37-76%, while paradoxically increasing leucovorin exposure by 14-60%. 4
- Administration with food results in a 34% decrease in peak tegafur concentration. 4
Toxicity Profile
Favorable Safety Characteristics
- UFT is notably well-tolerated compared to intravenous 5-FU regimens, with diarrhea as the dose-limiting toxicity. 5, 2
- Unlike IV 5-FU, UFT is not associated with significant myelosuppression, mucositis, hand-foot syndrome, or alopecia. 2
- Patients have decreased risk of toxicity-related hospitalization compared to IV regimens. 2
- Grade 3/4 toxicities include diarrhea (17%) and nausea/vomiting (11%). 3
Clinical Context and Limitations
Geographic Considerations
- UFT has been commercially available in Japan since 1983-1984 and is extensively studied in Asian populations. 5, 6
- Western guidelines note limited experience compared to capecitabine, making it a less preferred option in Europe and North America. 1
Relative Activity
- UFT's relative activity and safety compared to infusional 5-FU has not been definitively established in Western populations. 1
- The convenience of oral administration and reduced toxicity provide potential pharmacoeconomic advantages over IV regimens. 2