# Preoperative Chemoradiotherapy with Tegafur-Uracil, Capecitabine, or 5-Fluorouracil/Leucovorin for Rectal Cancer in an Asian Cohort: A Real-World Comparison from the Pre-TNT Era

## TL;DR

This study compares three chemotherapy regimens used with radiotherapy for rectal cancer in Asian patients, finding that all are similarly effective but with UFT causing fewer blood-related side effects.

## Contribution

The study provides real-world evidence on the effectiveness and safety of tegafur-uracil in preoperative rectal cancer treatment in Asia.

## Key findings

- All three chemotherapy regimens showed similar oncologic outcomes and tolerability.
- UFT caused fewer cases of low white blood cell counts compared to other regimens.
- Three-year survival rates were high with no significant differences among the regimens.

## Abstract

Most clinical trials of preoperative chemoradiotherapy for rectal cancer have used only two chemotherapy drugs: capecitabine or 5-fluorouracil/leucovorin (5-FU/LV). In many Asian countries, another oral drug, tegafur-uracil (UFT), is widely used in daily practice but has been less well-studied in this setting. We reviewed 79 Asian patients with rectal cancer who all received radiotherapy before surgery together with one of three chemotherapy regimens: UFT, capecitabine, or 5-FU/LV. We compared acute side effects, pathologic complete responses, downstaging, and survival after treatment. All three regimens were generally well-tolerated and showed no obvious differences in major oncologic outcomes, while UFT tended to cause fewer problems with low white blood cell counts. Our findings suggest that UFT is a reasonable, convenient, and cost-conscious oral option for older or frail patients and for real-world practice in Asian settings.

Preoperative concurrent chemoradiotherapy (CCRT) is an important treatment for locally advanced rectal cancer, but the choice of chemotherapy utilized with radiotherapy is inconsistent. Guidelines mainly recommend 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine, whereas tegafur-uracil (UFT) is widely used in Asia with limited comparative data. We evaluated UFT versus capecitabine and 5-FU/LV in an Asian real-world cohort. Between 2012 and 2019, 79 patients with biopsy-proven cT2–4N0–N2 rectal cancer received pelvic radiotherapy plus concurrent UFT (n = 31), capecitabine (n = 30), or 5-FU/LV (n = 18), followed by surgery. Endpoints included acute toxicity, pathologic complete response (pCR), T/N downstaging, overall survival (OS), and recurrence-free survival (RFS). Diarrhea was the most common toxicity (grade 1–2 in 68.4%). Neutropenia differed by regimen (UFT, 0%; capecitabine, 20.0%; 5-FU/LV, 16.7%), with one grade 3 event (5-FU/LV). The overall pCR rate was 17.7% (UFT, 16.1%; capecitabine, 23.3%; 5-FU/LV, 11.1%), and nodal downstaging was more frequent with capecitabine. After a median follow-up of 39.1 months, the 3-year OS and RFS were 88.9% and 68.9%, respectively, without significant survival differences among regimens. UFT-based long-course CCRT appears feasible and generally tolerable in routine Asian practice, with no clear signal of substantially worse pCR or survival outcomes in this retrospective cohort. These real-world data can inform individualized regimen selection.