Association between elemental concentrations and chemotherapy-related acute adverse events in patients with...

While environmental exposure to toxic elements, such as cadmium (Cd) and chromium (Cr), is known to impair general organ function, its specific impact on patients' tolerance to platinum (Pt)-based chemotherapy remains largely unexplored. This study aimed to determine whether pretreatment accumulation of specific trace elements is associated with the occurrence of acute adverse events (AEs) in patients with nasopharyngeal carcinoma (NPC) receiving platinum (Pt)-based chemotherapy.

A single-center, prospective, longitudinal study was conducted on 140 patients with NPC. Elemental concentrations measured before the initiation of chemotherapy (hereafter referred to as "pretreatment concentrations") of 13 elements (arsenic (As), calcium (Ca), Cd, cobalt (Co), Cr, copper (Cu), mercury (Hg), magnesium (Mg), nickel (Ni), lead (Pb), platinum (Pt), selenium (Se), and zinc (Zn)) and acute AEs for each chemotherapy cycle were recorded. Elemental concentrations were measured in blood (B) and urine (U) using inductively coupled plasma mass spectrometry (ICP-MS). Univariate and multivariate logistic regression analyses were performed to evaluate the associations between element levels and chemotherapy-related acute adverse events (AEs).

The study enrolled 140 patients with stage II (n = 2, 1.4%), III (n = 76, 54.3%), and IVA (n = 62, 44.3%) NPC. Moderate positive correlations (Spearman's correlation coefficients ranging from 0.2 to 0.7, p < 0.05) were observed between the concentrations of individual elements (such as Cd, Pb, and Cr) measured in paired whole blood and urine samples. NPC patients with high urinary Cr, blood Cd, and urinary Pb concentrations were more likely to experience higher incidences of thrombocytopenia (5% vs. 23%, p = 0.002), hepatotoxicity (40% vs. 60%, p = 0.028), and dysglycemia (46% vs. 74%, p < 0.001), respectively. In the multivariate adjusted logistic regression, blood Cd (OR = 3.65, 95% CI 1.38-9.64; p = 0.009) and urinary Cr (OR = 3.34, 95% CI 1.60-19.87; p = 0.007) were identified as independent predictors of hepatotoxicity and thrombocytopenia in NPC patients receiving Pt-based chemotherapy.

Pretreatment elevation of specific elements, particularly blood Cd and urinary Cr, was independently associated with a significantly increased risk of chemotherapy-related acute AEs. Specifically, blood Cd and urinary Cr were independent predictors of hepatotoxicity and thrombocytopenia in NPC patients undergoing Pt-based chemotherapy.