Optimize the dose of oxaliplatin for locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by radical surgery and adjuvant chemotherapy.

Background: Addition of oxaliplatin to capecitabine remains controversial for locally advanced rectal cancer (LARC). And cumulative oxaliplatin dose (COD) varied among clinical trials showing different therapeutic effects of this regimen. The objective of this study was to explore how COD affected tumor metastasis and patient survival.
Methods: Totally 388 patients diagnosed with stage cII-III rectal cancer and treated with neoadjuvant chemoradiotherapy followed by radical surgery plus adjuvant chemotherapy were consecutively enrolled into this study and retrospectively reviewed. After grouping by total chemotherapy cycle (TCC), influences of COD on adverse effects and patients' survivals were analyzed in each group. Univariate and multivariate survival analyses were performed through Kaplan-Meier approach and COX proportional hazards model, respectively. Age, gender, anemia, differentiation, carcinoembryonic antigen, carbohydrate antigen 19-9, pretreatment clinical stage and postsurgical pathologic stage were used as covariates.
Results: COD < 460 mg/m ² emerged as an independent predictor of poorer overall, metastasis-free and disease-free survivals, in patients treated with TCC ≤ 7. The hazard ratios were 1.972, 1.763 and 1.637 (P values were 0.021, 0.028 and 0.041), respectively. But it was note-worthy that COD ≥460 mg/m ² increased incidence of acute toxicities from 38.4 to 70.8% (P < 0.001). And in patients treated with TCC ≥ 8, COD failed to be a prognosticator.
Conclusions: For LARC patients treated with insufficient TCC (≤ 7), oxaliplatin of ≥460 mg/m ² might be needed to improve survival, though it might resulted in more acute toxicities.