Phase 2 Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-FU, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: ECOG 3204

Abstract

As previously reported, the neoadjuvant regimen of capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) for locally advanced rectal cancer resulted in a pathologic complete response (path CR) rate of 17%, which did not meet prespecified criteria of significant improvement; however, the effect of the intensified adjuvant regimen of 5-FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab is not reflected in path CR rate. The purpose of this report was to describe the 5-year oncologic outcomes of this regimen. Fifty-seven patients (pts) with resectable T3/T4 rectal adenocarcinoma were enrolled onto ECOG trial E3204 from 2006 to 2010. Preoperative treatment: capecitabine (825 mg/m2 BID M-F), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg D1, 15, 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8 – 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) Q2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). Recurrence-free survival (RFS) was measured from surgery to disease recurrence or death without recurrence among patients who underwent curative resection. Fifty-three of 57 enrolled pts were eligible and included in the analysis. Most patients were clinical (c)T3 (92%) and cN positive (64%). Of the 48 patients who underwent curative surgery, 26 (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80% (90% confidence interval (CI) [67%, 92%]). Only 2 patients experienced cancer recurrence, 1 distant (liver) and 1 locoregional (pelvic lymph nodes), respectively. Both of these patients are still alive. The 5-year cause specific survival rate was 100%. The 5-year RFS rate was 81% (90% CI [68%, 94%]). Despite the path CR primary endpoint of this trial not being reached, the 5-year OS and RFS rates were excellent; however, as previously reported, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. The notable disease control outcomes reported here may be due to patient selection issues, small patient numbers, the intensified neoadjuvant and/or adjuvant regimens, or a combination of factors; nonetheless, due to the lack of an improvement in the path CR rate, the substantial associated toxicity, and the negative phase 3 trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study.