| Summary: | BACKGROUND: 5-fluorouracil (FU) is commonly used in preoperative chemoradiation in locally advanced rectal cancer, but not all patients cooperate in taking the 5-day continuous infusion regimen. Raltitrexed (RA), a thymidylate synthase inhibitor, is one of the agents used in place of FU in such cases. We retrospectively compared the toxicity, tumor downstaging, pathologic response and relapse rate with bolus FU or RA during concurrent radiotherapy (RT) to assess the role of RA in place of FU. PATIENTS AND METHODS: We conducted a retrospective analysis of response rates and toxicity data on 59 patients diagnosed with locally advanced rectal cancer and treated with surgery following preoperative chemoradiation with either concurrent FU or RA between January 1999 and December 2004. RESULTS: Median follow-up was 38 months (range, 1–70). Ten patients (10%) had grade 3 gastrointestinal (GIS) toxicity during chemoradiation. The pathologic complete response rates were 6% with FU and 7% with RA (P=0.844), while 66.7% of patients treated with FU and 37.1% with RA had downstaging of the T stage after chemoradiation (P=0.026). The sphincter preservation rates were 45.8% with FU and 51.4% with RA (P=0.912). The 5-year local control rates were 79.2% for patients treated with RT+FU and 85.76% for patients treated with RT+RA (P=0.510). CONCLUSION: Compared with the RT+RA regimen, the incidence of downstaging was greater with RT+FU, but RT+FU was associated with a correspondingly greater rate of acute grade 2 GIS toxicity. However, no significant differences were seen in sphincter preservation, pathologic complete response, local control and distant recurrences rates among patients. FU seems to be the best therapeutic choice, while RA seems to be as effective as bolus FU.
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