CYP3A Activity in End-of-Life Cancer Patients Measured by 4β-Hydroxycholesterol/cholesterol Ratio, in Men and Women

Abstract

More than 50% of all drugs are metabolized by the cytochrome P450 3A enzyme (CYP3A). The aim of this study was to investigate if the CYP3A activity, measured by the endogenous marker 4β-hydroxycholesterol/cholesterol ratio (4β-OHC/C), is changed during the last weeks and days of life in men and women. To this end, serum samples from 137 deceased patients (median age 70 years) collected at a single time point 1-60 days before death, were analyzed and compared to 280 young (median 27 years), and 30 elderly (median age 70 years) non-cancer controls. There were no significant differences in the 4β-OHC/C ratio between men and women in end-of-life patients (p < 0.25). The median 4β-OHC/C was significantly higher in end-of-life male patients compared to both young (p < 0.0001) and elderly (p < 0.05) male controls. In a similar manner, 4β-OHC/C in end-of-life female patients was significantly higher compared to young and elderly female controls, p < 0.0001 and p < 0.001, respectively. There was no significant correlation between 4β-OHC/C and survival time. The results from this study suggest maintained CYP3A activity to the very last days of life and even a capacity of induction of the enzyme in end-of-life cancer patients.

Keywords: 25-hydroxyvitamin D; 4β-hydroxycholesterol/cholesterol; CYP3A-activity; cancer; end-of life; palliative care.

Figure 1

Differences in 4β-hydroxycholesterol/cholesterol ratio (4β-OHC/C) between (A) male and female patients (B) male cancer patients, young and elderly controls, and (C) female cancer patients, young and elderly controls.

Figure 2

Correlation between 4β-hydroxycholesterol/cholesterol ratio (4β-OHC/C) and survival time measured in days in (A) all patients (n = 137) (B) males (n = 69), and (C) females (n = 68). Statistical analysis was performed using Spearman’s rank test. r = Spearman’s r.