A phase II trial of neoadjuvant IMRT-based chemoradiotherapy followed by one cycle of capecitabine for stage II/III rectal adenocarcinoma

PURPOSE: Neoadjuvant chemoradiation has become the standard treatment in locally advanced rectal cancer (LARC) and improves local control. This study explored the feasibility of an intensified chemoradiation treatment followed by one cycle of capecitabine before surgery for LARC. METHODS AND MATERIALS: Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received intensity-modulated radiation therapy (IMRT) to the pelvis (total dose 44 Gy in 20 fractions), as well as concurrent oxaliplatin (50 mg/m(2) d1 weekly) and capecitabine (625 mg/m(2) b.i.d. d1–5 weekly). One cycle of capecitabine (1000 mg/m(2) b.i.d. d1–14) was given two weeks after the completion of concomitant chemoradiation, and radical surgery was scheduled six weeks after chemoradiation. RESULTS: Between October 2007 and November 2008, a total of 42 patients were enrolled in the study (median age 51 years; 31 male). Of these, 38 underwent surgical resection and 4 refused radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy. Fifteen patients underwent sphincter-sparing lower anterior resection. Six patients had a pathological complete response (pCR). The incidence of grade 3 hematologic, gastro-intestinal, and skin toxicities were 4.7%, 14.3%, and 26.2%, respectively. Grade 4 toxicity was not observed. Surgical complications (incisional infection within 2–3 weeks after surgery) were observed in 5 patients. Good responders (defined as TRG 3–4) had a significant difference in DFS (81.6% vs. 16.8%, respectively; p = 0.000) and OS (83.9% vs. 40.7%, respectively; p = 0.007) compared to those who were evaluated as TRG 1–2. CONCLUSIONS: Our study indicates that neoadjuvant chemoradiation followed by one cycle of capecitabine before surgery has a good treatment efficacy, with only mild toxicities associated with chemoradiation and acceptable surgical complications. Treatment response was an early surrogate marker and correlated to oncologic prognosis.