Improved incidence of pT0 downstaged surgical specimens in locally advanced rectal cancer (LARC) treated with induction oxaliplatin plus 5-fluorouracil and preoperative chemoradiation

Abstract

Purpose: To compare efficacy in terms of pathologic response in LARC patients treated with preoperative chemoradiation, with or without a short-intense course of induction oxaliplatin.Patients and Methods: From 05/98 to 10/02, 114 patients were treated with preoperative chemoradiation (4500–5040cGy + oral Tegafur 1200mg/day) for cT3-4N+/xM0 rectal cancer. Starting 05/01, 52 consecutive patients additionally received induction FOLFOX-4, oxaliplatin (85mg/m2 iv d1), 5-FU (400mg/m2 iv bolus d1) and 600mg/m2 iv continuous infusion in 22h with leucovorin (200mg iv) d1 and d2, every 15 days (2 cycles), followed by the previously described Tegafur chemoradiation regime. Surgery was performed in 5–6 weeks. Pathological assessment investigated post-treatment T and N status in the rectal wall and peri-rectal tissues.Results: Patients, tumor and treatment characteristics were comparable between groups. Incidence of pT0 specimens was significantly increased by induction FOLFOX-4 (P = 0.006). Total T and N downstaging were 58% versus 75% and 42% versus 40%, respectively (P = ns). T downstaging of ≥2 categories was significantly superior in FOLFOX-4 group (P = 0.029).Conclusions: Short-intense induction FOLFOX-4 significantly improves pathologic complete response in LARC patients treated with tegafur-sensitized preoperative chemoradiation. The 44% rate of pT0-1 specimens observed in the oxaliplatin group should impulse innovative surgical approaches to promote ano-rectal sphincter conserving protocols.