Good Outcome With Neoadjuvant Chemoradiation and Local Excision in Clinical T2,N0 Distal Rectal Cancer
In a multi-institutional phase II trial (ACOSOG Z6041) reported in The Lancet Oncology, Garcia-Aguilar et al found that neoadjuvant chemoradiotherapy and local excision was associated with an acceptable disease-free survival rate, albeit not so high as anticipated, in patients with clinical stage T2,N0 distal rectal cancer.
Study Details
The study included 79 patients treated at 26 American College of Surgeons Oncology Group institutions between May 2006 and October 2009 who had T2,N0 rectal adenocarcinoma < 4 cm in greatest diameter, involving < 40% of the rectum circumference, and located within 8 cm of the anal verge. All patients were to undergo local excision following neoadjuvant chemoradiotherapy.
Neoadjuvant chemoradiotherapy consisted of capecitabine at an initial dose of 825 mg/m² twice daily on days 1 to 14 and 22 to 35, oxaliplatin at 50 mg/m² at weeks 1, 2, 4, and 5, and radiation 5 days a week at 1.8 Gy per day for 5 weeks to a dose of 45 Gy followed by a boost of 9 Gy for a total dose of 54 Gy. Due to adverse events during chemoradiotherapy, the capecitabine dose was reduced to 725 mg/m² twice daily 5 days per week for 5 weeks and the radiation boost was reduced to 5.4 Gy for a total dose of 50.4 Gy.
The primary endpoint was 3-year disease-free survival in the intent-to-treat population and in the per-protocol population, consisting of patients who completed chemotherapy and radiation and had ypT0, ypT1, or ypT2 tumors and negative resection margins. Based on existing data, the investigators estimated that 3-year disease-free survival probability of at most 80% would be deemed unacceptably low and a probability of at least 91% would be considered very promising.
Disease-Free Survival
Among the 79 patients, 72 were included in the per-protocol analysis; among those excluded, 2 had no surgery, 1 had total mesorectal excision, 1 had a positive margin, and 3 had ypT3 tumors.
Median follow-up was 56 months for all patients. Estimated 3-year disease-free survival was 88.2% (95% confidence interval [CI] = 81.3%–95.8%) in the intent-to-treat group and 86.9% (95% CI = 79.3%–95.3%) in the per-protocol group. Among all patients, the local recurrence rate was 4% at the end of follow-up.
Among all patients, 29% had grade 3 gastrointestinal adverse events, 15% had grade 3 or 4 pain, and 15% had grade 3 or 4 hematologic adverse events during chemoradiation. Among the 77 patients who had surgery, 8% had grade 3 pain, 4% had grade 3 or 4 hemorrhage, and 4% had gastrointestinal adverse events.
The investigators concluded: “Although the observed 3-year disease free survival was not as high as anticipated, our data suggest that neoadjuvant chemoradiotherapy followed by local excision might be considered as an organ-preserving alternative in carefully selected patients with clinically staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection.”
Julio Garcia-Aguilar, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Lancet Oncology article.
The study was funded by the National Cancer Institute and Sanofi-Aventis. For full disclosures of the study authors, visit www.thelancet.com/journals/lanonc.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
