The Role of UFT in Metastatic Colorectal Cancer

Abstract

5-Fluorouracil (5-FU) has been the most widely used chemotherapeutic agent for metastatic colorectal cancer (mCRC) and 5-FU combination therapy improves efficacy compared with monotherapy. The oral fluoropyrimidine UFT (tegafur-uracil) with leucovorin (LV) improves tolerability and has replaced 5-FU in many regimens. The efficacy and tolerability of UFT with LV in the first-line treatment of mCRC has been demonstrated in a number of phase II studies. In two phase III studies, UFT with LV has been shown to have comparable efficacy and improved tolerability versus intravenous bolus 5-FU, with very few cases of hand-foot syndrome (HFS). Indirect comparisons of UFT and capecitabine suggest that they are comparable in terms of survival. In first-line treatment, UFT in combination with oxaliplatin (TEGAFOX) or irinotecan (TEGAFIRI) is effective and well tolerated, with similar efficacy and tolerability to the corresponding 5-FU- and capecitabine-based combinations, but with a lower incidence of HFS. Alternating cycles of TEGAFOX and TEGAFIRI are effective and well tolerated, and the combination of TEGAFIRI and the targeted monoclonal antibody cetuximab has shown promising activity, similar to that of FOLFIRI plus cetuximab. UFT can be considered a rational replacement for intravenous 5-FU in the first- and second-line treatment of patients with mCRC.

Circulating Tumor Cell Enumeration in a Phase II Trial of a Four-Drug Regimen in Advanced Colorectal Cancer

“…38 The rationale for adopting UFT in the present study was the comparable clinical efficacy data with (the now more commonly used) capecitabine but with a better tolerability profile. [39][40][41] The incidence of palmar-plantar erythema was low; however, we acknowledge that this agent is no longer in routine use, and future studies will need to incorporate an alternative 5-FU as a backbone of the therapy. Our CTC data confirmed that enumeration of CTCs at baseline is prognostic for OS in patients with ACRC, consistent with data from previous reports.…”

Phase I/II Study of Preoperative Concurrent Chemoradiotherapy with S-1 for Locally Advanced, Resectable Rectal Adenocarcinoma

“…However, the protracted venous infusion of 5-FU requires in-dwelling catheters and outpatient ambulatory infusion pumps that are associated with potential risks of infection and thrombosis and are inconvenient for the patients. Consequently, oral fluoropyrimidines, such as S-1, UFT and capecitabine, have been developed as a therapeutic alternative to the protracted venous infusion of 5-FU [6,7,8]. …”

Phase II study on early start of chemotherapy after excising primary colorectal cancer with distant metastases (Pearl Star 02)

“…Continuous infusion avoided the high serum 5‐FU levels that could be observed with bolus injection dosage and may be efficacious in CRC without increasing anastomotic leakage. The oral fluoropyrimidine drug, capecitabine, evolved to ameliorate patient convenience and tolerability and has replaced continuous infusions of 5‐FU in many chemotherapy regimens 33. Capecitabine appears to be a promising substitute to continuous infusions of 5‐FU, and pharmacokinetic researchers have reported that successive oral administration provided a steady‐state 5‐FU concentration that was comparable with that achieved by a 5 day continuous infusion 34, 35.…”