Capecitabine (X) chemoradiation (CRT) in the preoperative treatment of patients (pts) with rectal adenocarcinomas: A phase II GERCOR trial

Abstract

3538 Background: X CRT is attractive since the active metabolite, 5-FU, is a potent radiosensitizer. There is a strong preclinical rationale based on higher TP levels in tumor, which are further upregulated with radiation, TP being the final metabolising enzyme of X to 5-FU. X has potential to enhance the results of rectal cancer CRT. A phase I study recommended X 825 mg/m2 twice daily with pelvic RT. Methods: We conducted a multicenter, phase II trial to evaluate the efficacy of pre-operative X CRT in pts with adenocarcinoma of the lower or middle third of the rectum, suitable for curative surgery, T3-T4 or N+. Pts had no inflammatory bowel disease, adequate biological parameters, written informed consent. RT delivered 45 Gy in 25 fractions over 5 weeks. X was taken 7 days/week, 825 mg/m2 morning and evening, throughout RT. Surgery was 5 to 7 weeks after the end of RT. The primary endpoint was complete histological response rate; secondary endpoints were downstaging and tolerability. Results: From July 2002 to June 2003, 51 pts were included, 17 women and 34 men, median age 62 years [35–78], with median KPS (Karnofsky) 90% [80–100]. Sixty three percent of tumors involved the lower third of the rectum, 45% were fixed.. Initial endoscopic US/MRI classification was T2, T3, T4 in 4, 45 and 1 cases respectively, 1 pt was T3 on CT evaluation. Median delivered dose was 45 Gy [39,6–45 Gy] in 32 to 44 days. RT was temporarily interrupted in 3 pts (2 G3, 1 G2 skin reaction + G2 diarrhoea in 1) and X stopped before the end of RT in 2 pts (2 G2 hand-foot syndrome + G3 diarrhoea in 1). Adverse events were mostly gastrointestinal (10 pts G2, 3 pts G3 diarrhoea) and cutaneous (8 pts G2 and 2 pts G3 local skin reaction); 3 pts experienced G2 hand-foot syndrome. Fifty pts had surgery (29 conservative), 1 refused. Histopathology revealed 24% complete responses (95% CI 12–36%), 12% persistence of only minimal tumor cell foci and 23% additional T downstaging. Resection margins were tumor free in 100%. Conclusions: X CRT is well tolerated and efficacy supports further exploration, as a single agent and as part of new therapeutic strategies with chemo- and biological therapies. No significant financial relationships to disclose.