Systematic review and meta-analysis of 24 studies (15 RCTs, 9 retrospective cohorts; n=30,395) comparing reduced oxaliplatin exposure (ROE) vs. standard-duration oxaliplatin-based therapy in GI cancers, with primary endpoints of DFS, PFS, and OS, and secondary endpoints of CIPN and high-grade adverse events.
ROE did not significantly differ from standard therapy in survival outcomes across adjuvant CRC (DFS HR 1.06, OS HR 0.99), metastatic CRC (PFS HR 1.11, OS HR 1.06), or metastatic gastroesophageal cancers (PFS HR 0.82, OS HR 0.90), but meaningfully reduced grade ≥3 CIPN (OR 0.34, 95% CI 0.21–0.57) and grade ≥3 AEs (OR 0.67, 95% CI 0.48–0.92).
Evidence is driven predominantly by colorectal cancer, with limited data in pancreatic and gastroesophageal cancers; 9 of 24 included studies were retrospective cohorts, introducing potential selection bias; meta-analysis cannot exclude modest survival detriments from ROE given wide confidence intervals in some subgroups.
Clinicians can plan a deliberate reduction in total oxaliplatin exposure across GI cancers to cut neurotoxicity and high-grade adverse events without a statistically significant loss in survival benefit. This strategy is best supported in colorectal cancer; caution is warranted in gastroesophageal and pancreatic settings where data remain sparse.
