(ChemotherapyAdvisor) – Adding oxaliplatin therapy to 5-fluoropyrimidine (5-FU)-based radiochemotherapy modestly improves pathologic complete response (pCR) in locally-advanced rectal cancer, according to a meta-analysis of data from four randomized phase 3 clinical trials. The analysis was published October 11 in the European Journal of Cancer.
Adding weekly oxaliplatin to 5-FU-based neoadjuvant chemoradiotherapy “has significant but modest effect on response of the primary rectal tumor and regional lymph nodes, and significant and a strong effect of reducing peri-operative metastases,” reported senior author Pei-Rong Ding, MD, of the Department of Radiation Oncology at Sun Yat-sen University Cancer Center in Guangzhou, China, and coauthors.
Together, the analyzed data from four clinical trials represented 3,863 patients. One of the source trials had found improved pCR among patients administered oxaliplatin in addition to 5-FU-based chemoradiotherapy, while three other trials did not report significantly superior pCRs among these patients. The authors pooled data from all four studies to address resulting uncertainty.
They found that when data from all studies were pooled, the odds ratio for pCR was superior in oxaliplatin-containing regimens (OR 1.20 [95% CI: 1.01-1.42]; P=0.04). While that pCR improvement was statistically significant, however, it represented a modest absolute difference of 2.5%, the authors noted.
Peri-operative metastasis rates were significantly lower among patients receiving oxaliplatin plus 5-FU-based chemoradiotherapy, the authors of the meta-analysis reported (OR = 0.51 [95% CI: 0.34-0.77]; P=0.001).
Adding oxaliplatin increased the risk of adverse events associated with 5-FU-based chemoradiotherapy, the meta-analysis showed. Grade ¾ toxicity rates ranged from 15.4% to 24.7% among patients receiving oxaliplatin plus 5-FU-chemoradiotherapy, and ranged from 6.6% to 20.0% among patients receiving 5-FU-chemoradiotherapy without oxaliplatin, the authors reported (OR 2.29 [95% CI: 1.31-4.00];P=0.004).
Patients receiving oxaliplatin were less likely to receive full-dose radiotherapy than were patients treated with 5-FU alone, possibly a result of higher adverse event rates among patients receiving oxaliplatin, the authors of the meta-analysis cautioned.