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Published on: February 12, 2017
Reduced oxaliplatin exposure in gastrointestinal cancers: A systematic review and meta-analysis
Wallace Klein Schwengber1, Fares Jamal2, Luis Felipe Leite da Silva3
1Internal Medicine Division, Mayo Clinic, Phoenix, AZ 85054, USA.
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.
