Pharmacokinetic and pharmacogenomic profile of capecitabine and oxaliplatin in a patient with gastric cancer undergoing hemodialysis: a case report

Purpose: Anticancer therapy for patients with gastric cancer on hemodialysis is challenging owing to varying pharmacokinetics and a lack of clinical trial data. This study aimed to evaluate the efficacy and safety of the capecitabine plus oxaliplatin (CapeOX) regimen in a 73-year-old male Japanese patient with stage IV gastric cancer (human epidermal growth factor receptor 2 negative) undergoing hemodialysis. Methods: The selected chemotherapy regimen was approximately 50% dose of CapeOX (capecitabine 1500 mg/day on days 1–14 and oxaliplatin 100 mg/day 2-h infusion on day 1) every 3 weeks. Data on plasma drug concentrations, metabolic enzyme genetic polymorphisms, and clinical outcomes were analyzed. Results: Anticancer therapy initially controlled the tumor; however, disease progression and cumulative peripheral neuropathy led to discontinuation after 17 cycles (approximately 12 months of treatment). Oxaliplatin exhibited a rebound increase after each dialysis session (dialyzer clearance [CL_dial]: median, 44.12 [interquartile range {IQR}: 24.89 − 70.08] mL/min; hemodialysis removal rate: median, 35.98% [IQR: 19.63 − 54.45]. α-fluoro-β-alanine, the final metabolite of capecitabine, accumulated substantially, although approximately half of them was removed by hemodialysis (CL_dial: median, 61.32 [IQR: 24.89 − 70.08] mL/min; hemodialysis removal rate: median, 47.98% [IQR: 44.74 − 50.29]). The UPB1 intronic variant and a DPYD missense mutation (1627 A > G) were detected. The DPYD variant likely influenced 5-fluorouracil metabolism, as its area under the concentration-time curve from 0 to 12 h was comparable to the standard dosage. Conclusion: These findings suggest that appropriate dose reduction and genetic screening might be considered part of chemotherapy guidance to improve safety and effectiveness for patients with advanced gastric cancer undergoing hemodialysis.