Reduced oxaliplatin exposure in gastrointestinal cancers: A systematic review and meta-analysis
In brief
Reduced oxaliplatin exposure linked to 66% lower odds of severe neuropathy
Across 24 studies involving 30,395 patients, reduced oxaliplatin exposure was associated with lower odds of severe nerve damage and other high-grade side effects. Survival outcomes were not significantly different from standard-duration treatment, suggesting less exposure could reduce toxicity without a detected survival cost. Most evidence came from colorectal cancer, so results in pancreatic and gastroesophageal cancers remain uncertain.
- Journal
- Cancer treatment reviews (Q1)
- Published
- 23 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Wallace Klein Schwengber, Fares Jamal, Luis Felipe Leite da Silva, Diana Segovia, Abdullah Alsulaiman, Ayla Kouli, et al.
- PMID
- 42801795
- DOI
- 10.1016/j.ctrv.2026.103215
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 2 October 2026): Systematic review/meta‑analysis of reduced oxaliplatin exposure
Abstract
BACKGROUND: Oxaliplatin chemotherapy-induced peripheral neuropathy (CIPN) is dose-limiting, severe, and often permanent. Whether reduced oxaliplatin exposure (ROE) preserves efficacy while limiting toxicity across gastrointestinal (GI) cancers remains uncertain. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of studies comparing ROE strategies versus standard-duration oxaliplatin-based therapy in GI malignancies. Random-effects meta-analyses were performed according to PRISMA guidelines. Primary endpoints were disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). Secondary endpoints included grade 2 CIPN, grade ≥ 3 CIPN, and any grade ≥ 3 adverse events (AEs). RESULTS: Twenty-four studies (15 randomized trials, 9 retrospective cohorts) involving 30,395 patients were included; 13,348 received ROE and 17,047 standard therapy. In adjuvant colorectal cancer, ROE was not associated with differences in DFS [HR 1.06, 95% CI 0.97-1.17; P = 0.15] or OS (HR 0.99, 95% CI 0.90-1.09; P = 0.80). In metastatic colorectal cancer, no differences were observed in PFS (HR 1.11, 95% CI 0.99-1.25; P = 0.07) or OS (HR 1.06, 95% CI 0.92-1.23; P = 0.33). In metastatic gastroesophageal cancers, PFS (HR 0.82, 95% CI 0.34-1.99; P = 0.44) and OS (HR 0.90, 95% CI 0.67-1.21; P = 0.26) were also not statistically different. ROE reduced grade 2 CIPN (OR 0.46, 95% CI 0.25-0.84), 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). CONCLUSIONS: ROE was not associated with statistically significant differences in survival outcomes but with reduced neurotoxicity and high-grade AEs, supporting planned limitation of oxaliplatin exposure to improve the therapeutic index across GI malignancies. The evidence was driven predominantly by colorectal cancer, while data in pancreatic and gastroesophageal cancers remain limited.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.