Long-Term Follow-up Shows Favorable Overall Survival Rates With Concurrent Neoadjuvant Chemoradiotherapy Regimens in Rectal Cancer
Patients with locally advanced rectal cancer who receive neoadjuvant radiation therapy with either irinotecan plus capecitabine or oxaliplatin plus capecitabine have a 4-year overall survival rate of 85% and 75%, respectively, according to a study reported by Wong et al in the International Journal of Radiation Oncology • Biology • Physics. This study is a secondary endpoint analysis of Radiation Therapy Oncology Group (RTOG) 0247, originally published in 2012, to evaluate long-term survival outcomes and patterns of failure.
RTOG 0247 was a randomized, phase II multicenter trial of patients with locally advanced (T3 and T4) rectal cancer treated with neoadjuvant chemoradiation from March 2004 to February 2007. The primary endpoint analysis of RTOG 0247 examined the pathologic complete remission rates of two concurrent neoadjuvant chemotherapy regimens to determine which regimen should be studied further. The initial results demonstrated that patients who received irinotecan plus capecitabine had lower pathologic complete response rates (10% compared to 21% for those who received oxaliplatin plus capecitabine).
RTOG 0247 Details
The study accrued 146 patients from 59 institutions from March 2004 to February 2007. All patients received preoperative pelvic radiation therapy of 50.4 Gy over 5.5 weeks, with 45 Gy delivered in 25 fractions (1.8 Gy per fraction, five fractions per week for 5 weeks) and a boost of 5.4 Gy in three fractions. Patients were randomly assigned to two chemotherapy treatment arms concurrent to their radiation therapy: Patients in arm 1 received concurrent chemotherapy consisting of four doses of irinotecan (50 mg/m2 IV weekly) and capecitabine (1,200 mg/m2/d orally Monday through Friday during radiation therapy). Patients in arm 2 received concurrent chemotherapy consisting of five doses of oxaliplatin (50 mg/m2 IV weekly) and capecitabine (1,600 mg/m2/d orally Monday through Friday during radiation therapy).
All patients in each arm had surgery 4 to 6 weeks after completion of radiation therapy, and all patients in both arms had postoperative chemotherapy with FOLFOX (fluorouracil, leucovorin, oxaliplatin) 4 to 6 weeks after surgery.
Both arms of the study were temporarily closed in January 2005 due to excessive gastrointestinal adverse events. The study reopened in April 2005 with an amended chemotherapy regimen. One hundred and four (104) patients, 52 in each arm, were eligible and included in this analysis. Eligible patients were at least 18 years old with a median age of 57 years; had clinical stage T3 or T4, potentially resectable adenocarcinoma of the rectum originating ≤ 12 cm from the anal verge without evidence of distant metastasis; had Zubrod performance of zero to two; and had adequate hematologic, renal, cardiac, and hepatic function.
Patient evaluations occurred weekly during concurrent chemotherapy and radiation therapy, before surgery and before each cycle of postoperative chemotherapy. Follow-up was conducted every 3 months for the first 2 years post-treatment, every 6 months for the next 3 years, and annually thereafter. The median follow-up for patients in arm 1 was 3.77 years (range = 0.19–5.23 years), and the median follow-up for patients in arm 2 was 3.97 years (range = 0.44–5.15 years).
4-Year Follow-up
The new study’s analysis of RTOG 0247’s long-term data found that at 4-year follow-up, patients in arm 1 (irinotecan plus capecitabine) had an overall survival rate of 85%, a disease-free survival rate of 68%, a local-regional failure rate of 16%, a distant failure rate of 24% and a second/new primary failure rate of 2%. At 4-year follow-up, patients in arm 2 (oxaliplatin plus capecitabine) had an overall survival rate of 75%, a disease-free survival rate of 62%, a local-regional failure rate of 18%, a distant failure rate of 30%, and a second/new primary failure rate of 6%. All measures had a 95% confidence interval.
“Our new analysis of RTOG 0247 provides us with favorable efficacy results of two preoperative chemotherapy regimens used in conjunction with radiation therapy protocols,” said Neal J. Meropol, MD, coauthor of the study, and Chief of the Division of Hematology and Oncology at University Hospitals Case Medical Center and Case Western Reserve University in Cleveland. “These favorable long-term survival rates confirm that both of these concurrent chemoradiotherapy regimens followed by surgery can be a highly curative approach for patients with localized rectal cancer, despite the low pathologic complete response results we reported in 2012. It is important to find new biomarkers beyond the local remission rate that can help us determine which patients will be cured and who may benefit from more aggressive therapy following chemoradiation.”
Dr. Meropol is the corresponding author for the International Journal of Radiation Oncology • Biology • Physics.
The study was supported by grants from the Radiation Therapy Oncology Group, the National Cancer Institute, and Roche Laboratories. The study authors reported no potential conflicts of interest.
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