(S028) Sequential Short-Course Radiotherapy and FOLFOX Chemotherapy as Preoperative Therapy for Rectal Cancer Provides Increased DFS Compared With Historical Controls

April 15, 2014

To compare rates of pathologic response, downstaging, local control, and treatment-related toxicity in patients treated in a prospective phase II trial of preoperative short-course radiotherapy and sequential FOLFOX (folinic acid, fluorouracil, oxaliplatin) chemotherapy with patients treated at our institution with preoperative long-course chemoradiotherapy and adjuvant chemotherapy.

Stephanie Markovina, MD, PhD, Shariq Khwaja, MD, PhD, Todd DeWees, PhD, Steven Hunt, MD, Benjamin Tan, MD, Robert Myerson, MD, PhD, Parag Parikh, MD, Jeff Olsen, MD; Washington University

Objective: To compare rates of pathologic response, downstaging, local control, and treatment-related toxicity in patients treated in a prospective phase II trial of preoperative short-course radiotherapy and sequential FOLFOX (folinic acid, fluorouracil, oxaliplatin) chemotherapy with patients treated at our institution with preoperative long-course chemoradiotherapy and adjuvant chemotherapy.

Background: A phase II study was recently completed at our institution in which patients with clinical (c) T3 and T4 rectal adenocarcinoma received short-course radiotherapy, followed by 4 cycles of FOLFOX chemotherapy as “near-total” neoadjuvant therapy for rectal cancer. In this analysis, we compared outcomes for patients treated with a near-total neoadjuvant approach with similar patients treated at our institution with standard-of-care preoperative concurrent long-course chemoradiotherapy and postoperative chemotherapy (standard of care).

Materials and Methods: A total of 80 patients with cT3–T4, any N, and any M planned for resection of the primary tumor were enrolled on the institutional phase II study of preoperative short-course radiotherapy (25 Gy to the involved mesorectum, 20 Gy to elective nodes in five fractions), followed by 4 cycles of mFOLFOX6 chemotherapy before extirpative surgery. Postoperatively, treatment with 6–8 cycles of adjuvant FOLFOX was suggested at the discretion of the treating medical oncologist. A comparison cohort of 92 patients was identified with locally advanced rectal cancer that was treated at our institution with standard-of-care therapy. These patients had cT3 or cT4 rectal adenocarcinoma and received preoperative concurrent chemoradiotherapy to 45–54 Gy to similar volumes, followed by extirpative surgery. All patients in the comparison group also received postoperative chemotherapy. Kaplan-Meier with log-rank analysis was used to compare local control (LC) and disease-free survival (DFS) outcomes between the two groups, and non-parametric Mann-Whitney Wilcoxon rank sum was used to compare patient and treatment characteristics.

Results: Tumors were converted to ypT0 in 28% in the study cohort compared with 17% of patients in the control cohort (P = .26). T-downstaging was achieved in 68% of patients in the study cohort compared with 50% in the control cohort (P = .015). Median follow-up was 25 months (range: 4.6–46.5 mo) for the study cohort and 16 months (range: 3.9–72 mo) for the control cohort. For all evaluable patients, the 2-year LC was 97% and 96% in the study cohort and control cohort, respectively (P = .89). For all patients with cM0 disease, 2-year DFS was 94% vs 71% (P = .002) for the study vs control cohorts, respectively. The rate of acute GI toxicity of grade 3 and higher was 9% in the study cohort compared with 21% in the control cohort.

Proceedings of the 96th Annual Meeting of the American Radium Society - americanradiumsociety.org