965 Platinum-DNA adducts in peripheral blood leukocytes of patients receiving cisplatin- or carboplatin-based chemotherapy. Correlation with cisplatin in vitro treatment and with clinical activity

Abstract

Platinum (Pt)-DNA adducts by means of Inductively Coupled Plasma Mass Spectroscopy (ICPMS), were determined in peripheral blood leukocytes of 46 patients treated with Cisplatin- or Carboplatin-based chemotherapy, before the beginning of chemotherapy, and at 1 h and 24 h after the end of Cisplatin (or Carboplatin) infusion on each 1st and 3rd chemotherapy cycle. In basal samples Pt-DNA adducts were never detected. In 33 patients no correlation was found between the response to chemotherapy and the Pt-DNA adducts levels. In 20 patients, Pt-DNA adducts were determined in peripheral blood leukocytes withdrawn before the beginning of chemotherapy and incubated in vitro with Cisplatin (15 μg/ml in RPMI medium). In these leukocytes median Pt-DNA adducts was 8.64 fmol/ug of DNA (range = 1.6–25.4). A significant correlation was found between adducts formation in vitro and, in vivo at the 1 h after chemotherapy time point (r = 0.664; P = 0.0113); it was lost at the 24 h after chemotherapy time point (r = 0.241; P = 0.305). No correlation was found between in vitro adducts formation and response.