Risk assessment of heavy metal toxicity induced by platinum accumulation in tumor patients

Abstract

Background. Many studies have focused on adverse reactions caused by platinum drugs but neglected subsequent toxicities and the mechanisms during patient recovery after chemotherapy with different platinum drugs, which need attention because of the heavy metal platinum. Objectives. We aimed to explore the correlations between platinum accumulation, hematological indices, and clinical toxicity in patients after a metabolism period following platinum drug chemotherapy, to better understand real-world clinical toxicity caused by platinum accumulation. Methods. We enrolled patients receiving platinum chemotherapy, specifically cisplatin, oxaliplatin, or carboplatin. On the 25th day post-chemotherapy, we measured serum platinum concentrations and hematological indices, documented clinical toxicities, and subsequently performed correlation analyses. Results. The serum platinum concentrations in oxaliplatin-, cisplatin-, and carboplatin-treated patients were 208.60, 349.15 and 211.30 µg/L (χ2 = 51.755, p < 0.001), respectively. Mediation effect analysis showed that decreased erythrocyte, hemoglobin and glutamic-pyruvic transaminase individually mediated 21.39, 12.0 and 10.94%, respectively, of the platinum positive effect on fatigue. Decreased erythrocyte counts mediated 5.89%, while increased creatinine mediated 5.2% of the platinum positive effect on adverse reactions. The cutoff values of hematological indices, the risk of adverse reactions and fatigue were also obtained in this research which will be applied in clinical practice. Discussion and Conclusions. Platinum accumulation, by disrupting the red blood cell system and liver and kidney function, influences fatigue severity and common adverse reactions in patients during the post-chemotherapy recovery period.