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

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 (4500-5040 cGy + oral Tegafur 1200 mg/day) for cT 3-4 N +/x m o rectal cancer. Starting 05/01, 52 consecutive patients additionally received induction FOLFOX-4, oxaliplatin (85 mg/m 2 iv d1), 5-FU (400 mg/m 2 iv bolus d1) and 600 mg/m 2 iv continuous infusion in 22 h with leucovorin (200 mg 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 pT o 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 pT o-1 specimens observed in the oxaliplatin group should impulse innovative surgical approaches to promote ano-rectal sphincter conserving protocols.