A Single-Institution Phase Ii Trial Of Five Fractions Of Radiotherapy Followed By Four Courses Of Folfox Chemotherapy As Preoperative Therapy For Rectal Adenocarcinoma.

553 Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the known benefits of preoperative RT on local response/control, (2) provide for preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT. Methods: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for surgery, provided the response was sufficient. Preoperative treatment was 5 fractions RT (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of mFOLFOX6. Postoperative CT was at the discretion of the medical oncologist. The principal objectives are to demonstrate that this regimen can achieve T stage down staging (ypT < cT) and acute grade 3+ gastrointestinal (GI) morbidity equal to or better than historical controls. Results: Accrual opened late 2009, with 60 patients enrolled through 8/2011. Forty-six have had sufficient time to proceed to surgery with 4 having grade 3 preoperative GI morbidity. Two cases are inevaluable for response: one withdrew consent prior to CT and one received no surgery due to progression of cM1 disease (with local response). The 44 evaluable cases included 4 cT4 and 40 cT3; 32 (73%) cN+, 4 cM1. At surgery 33 (75%) had ypT0-2 residual disease including 13 (30%) ypT0, 14 (32%) were ypN+. Cases were sub-analyzed by whether disease was too advanced for the upcoming ACOSOG preoperative FOLFOX vs. 5FU-RT trial. By ACOSOG eligibility, response rates were (eligible first, ineligible second) ypT0: 10/22 (45%) vs. 3/22 (14%) (p = 0.05), ypT0-2: 19/22 (86%) vs. 14/22 (64%) (p = NS). Conclusions: This regimen achieves high response rates with acceptable morbidity. The response for ACOSOG eligible cases meets pre-determined stopping criteria for proceeding to a randomized trial. Our successor study will randomize to this regimen vs. FOLFOX alone for ACOSOG eligible cases, while initially continuing as a single arm trial for ACOSOG ineligible cases.