PLATINUM-DNA ADDUCT IN HEAD AND NECK-CANCER PATIENTS RECEIVING CISPLATIN AND CARBOPLATIN CHEMOTHERAPY

Sixteen patients with squamous cell carcinoma of the head and neck region were studied for the formation of platinum-DNA adduct in leukocyte DNA. Every patient received carboplatin and cisplatin, each given intravenously on day 1 of 21-day treatment cycles. Blood was obtained for DNA isolation 24 hours after treatment on cycles 1 and 2; and on the morning before cycle 2 of therapy (21 days after cycle 1 drug delivery). Adduct was measured by atomic absorbance spectrometry with Zeeman background correction. As has been shown in previous studies, adduct persistence and accumulation could be demonstrated in a portion of the cohort. Adduct removal from blood cell DNA during the 21 days of cycle number 1, was determined for 12 patients. In these patients, adduct removal was directly i-elated to clinical resistance to the cisplatin/carboplatin treatment regimen; and adduct removal was inversely related to leukocyte toxicity. These data demonstrate that changes in adduct levels with time may provide valuable information, in the study of the human in vivo biology of platinum-DNA damage and repair.