Neoadjuvant FOLFOX-bev, without radiation, for locally advanced rectal cancer.

Abstract

3511 Background: Preoperative 5FU-based chemo plus radiation therapy (RT) is standard for U.S. patients (pts) with locally advanced rectal cancer (RC). We conducted a pilot feasibility trial of pre-op FOLFOX-bevacizumab (bev) without RT for good-risk RC. Methods: Pts with clinical stage II-III RC (but not T4 tumors) who were candidates for sphincter-sparing surgery, were treated with 6 cycles of FOLFOX. Bev was included for cycles 1-4. Pts then were re-imaged and had repeat sigmoidoscopy with endorectal ultrasound (ERUS) performed by their surgeon to assess the primary tumor response. Those with stable/progressive disease were to be referred for pre-op 5FU plus RT, followed by surgery, and those with clinical regression were to have surgery without pre-op RT. Post-op 5FU plus RT was planned for any pts who did not have an R0 resection. Post-op chemo was left to investigator discretion, however 6 cycles of FOLFOX were recommended. The primary outcome was the R0 resection rate. Secondary outcomes were the pathologic CR rate, the 3-year disease free survival and local recurrence (LR) rate. Results: Of 31 pts accrued since March 2007, two were withdrawn from the study for cardiovascular toxicity (1 angina, 1 arrhythmia) after 1-2 cycles of FOLFOX-bev. Both had R0 resections. Of 29 who have completed pre-op chemo, all 29 had clinical regression and proceeded to surgery without pre-op RT. All 29 had R0 resections. Eight of 29 (27%) had a path CR. One pt with 14+ nodes and a close deep margin received post-op RT, and has since developed pulmonary mets. One pt with pathologic yT1N0 disease had high output ileostomy post-op but was discharged home in stable condition on day 10. He died suddenly 3 days later. Autopsy did not identify a cause. Local and distant recurrence rate data are immature; however thus far, there have been no LRs and 3 distant recurrences, all pulmonary. 26 patients remain alive and disease-free. Conclusions: Preliminary results of this pilot trial indicate that preoperative FOLFOX-bev chemo without RT achieves a high rate of R0 resections and path CRs in good risk RC. Further trials of non-RT-containing approaches are warranted. Supported by Genentech. No significant financial relationships to disclose.