The addition of oxaliplatin to capecitabine-based postoperative chemoradiotherapy (CRT) did not improve treatment efficacy and increased the risk for severe acute toxic effects in patients with locally advanced rectal cancer, according to a study in JAMA Network Open.
The multicenter, phase 3, randomized clinical trial enrolled patients with stage II or III rectal cancer from April 1, 2008, to December 30, 2015, with follow-up ending on December 31, 2019 (ClinicalTrials.gov Identifier: NCT00714077).
Participants were assigned randomly 1:1 to receive radiotherapy (RT) concurrently with capecitabine or with capecitabine and oxaliplatin. In the capecitabine with RT group, patients received postoperative concurrent CRT with capecitabine (1600 mg/m2) on days 1 to 14 and days 22 to 35. In the capecitabine and oxaliplatin with RT group, patients received postoperative concurrent CRT with capecitabine (1300 mg/m2) on days 1 to 14 and days 22 to 35, and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Both groups received adjuvant chemotherapy 4 weeks after CRT.
The primary endpoint was disease-free survival (DFS), defined as the time from randomization to first occurrence of locoregional recurrence, distant metastasis, or death from any cause.
A total of 589 patients were included in the study cohort — 294 patients in the capecitabine with RT group (median age, 55 years [IQR, 47-62 years]; 64.6% men) and 295 patients in the capecitabine and oxaliplatin with RT group (median age, 55 years [IQR, 47-62 years]; 62.7% men). About 76% of patients had stage III disease.
The median follow-up was 68 (IQR, 45-96) months. Among participants who received capecitabine with RT, 82 deaths or recurrence of cancer events (27.9%) occurred, and in the capecitabine and oxaliplatin with RT group 86 deaths or recurrence events (29.1%) occurred.
The capecitabine with RT group had a 3-year DFS of 76.3% vs 72.0% in the capecitabine and oxaliplatin with RT group; the 5-year DFS was 74.1% in the capecitabine with RT group vs 71.1% in the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P =.68).
The 5-year overall survival was 82.9% for the capecitabine with RT group and 82.4% for the capecitabine and oxaliplatin with RT group (HR, 0.93; 95% CI, 0.64-1.34; P =.70). The 5-year local recurrence-free survival was 92.9% for the capecitabine with RT group and 95.3% for the capecitabine and oxaliplatin with RT group (HR, 0.61; 95% CI, 0.31-1.22; P =.16).
A significant difference was observed between the 2 groups regarding grade 3 or 4 toxic effects (114 patients [38.6%] in the capecitabine and oxaliplatin with RT group vs 84 patients [28.6%] in the capecitabine with RT group; P =.01). Diarrhea or proctitis were the most common grade 3 to 4 events, occurring in 60 (20.5%) of patients who received capecitabine with RT and in 79 (26.9%) of those who received capecitabine and oxaliplatin with RT (P =.07).
Among several limitations, the researchers noted that they underestimated DFS in the control group, which led to a failure to reach the expected number of events. Additionally, the study was restricted to patients who received postoperative concurrent CRT.
“These findings suggest that capecitabine-based postoperative CRT could be considered to be an alternative type of multidisciplinary management of locally advanced rectal cancer for patients who did not receive neoadjuvant CRT,” stated the investigators.
Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Li N, Zhu Y, Liu L-Y, et al. Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs capecitabine for stage II to III rectal cancer: a randomized clinical trial. JAMA Netw Open. 2021;4(11):e2136116. doi: 10.1001/jamanetworkopen.2021.36116