Oxaliplatin (OXA), uracil/tegafur (UFT) and radiotherapy (RT) in operable rectal cancer (RC). Preliminary results of a multicenter phase II study

Abstract

3648 Background: In stage II-III RC, preoperative therapy (PT) with UFT (400 mg/m2, 5 days a week over 5 weeks) and RT (45Gy) produces downstaging (DS) in 54%, and pathological complete response (pCR) in 9% of patients (pts) as shown by our group [JCO 2004,22:3016]. Response is related with conservative surgery and survival. One way to improve response is to combine RT with the new actives and radiosensitizing agents, and OXA is one of them. The aim of this study is to asses the efficacy (pCR) and safety of PT with UFT/OXA and RT. Methods: The preliminary results of the phase I study of the combination were presented (ProcASCO, 2003). Dose-Limiting toxicity was diarrhea and the recommended dose for phase II study was: UFT 400 mg/m2, 5 days a week over 5 weeks combined with OXA: 85 mg/m2 d1, 15 and 29 and pelvic RT 50 Gy (1.8 Gy/day over 5 weeks and a weekly 1 Gy boost) in four defined fields. In the phase II study pts had to have non metastastic, middle or distal operable RC, uT3-T4 en endosonography. All pts were operated 5–6 weeks after PT. Results: Since October 2003, 22 pts (14M/8F) median age 59 (39–72) were accrued. To-date 13 (12uT3, 1uT4) are evaluable for pathological response and toxicity. The mean distance from pectineus line was 6 cms (2–11). There was DS (uT vs. pT) in 92% (12/13). 4pT0, 1pT1, 6pT2, 2pT3. There were 2 pT0N0 (pCR 15%) and in an additional 23% there were only residual microscopic foci. Efficacy results were reviewed by a second independent pathology evaluation. R0 resection was performed in all pts. Total dose of RT was achieved in 92%. Relative dose intensity for UFT was 92% and 98% for OXA. No G3–4 hematological toxicity was observed and G3 diarrhea was 15%. Conclusions: This regimen has a good activity with low toxicity profile. The addition of OXA more likely than RT boost seems to improve the efficacy of the UFT/RT regimen. Supported by an unrestricted grant by Sanofy-Aventis Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis