The measurement of cisplatin-DNA adduct levels in testicular cancer patients

Seventeen patients with ‘poor prognosis’ non-seminomatoustesticular cancer were monitored for formation of intrastrandbidentate N⁷-d(ApG)- and N⁷-d(GpG)- diammineplatinum adductsin peripheral blood cell DNA during the course of cisplatin-basedchemotheraphy. Adduct values from blood cell DNA samples werecompared with disease response data from the same individuals.Patients who received a dose of 40 mg/m² cisplatin for 5 daysgenerally formed more adducts than patients receiving 20 mg/m²for 5 days, and adduct levels ranged from 0 to approximately300 amol/µg DNA. Among the individuals who achieved acomplete response, the median adduct level was 170 amol/µgDNA and the mean was 162. Among the individuals who achieveda partial response, the median adduct level was 78 amol/ µgDNA and the mean was 83. Comparison of adduct levels betweenresponse groups using the Mann-Whitney test gave a two-sidedP value of 0.072 (one-sided P value 0.036). Of 11 patients forminghigh levels of adduct (>140 amol/µg DNA), 10 achieveda complete response; this compares with two complete respondersin the group of six patients forming low levels (<100 amol/µg DNA) of adduct (P = 0.055, two-sided Fisher exact test).We conclude that cisplatin-DNA adduct formation in peripheralblood cell DNA correlates with the occurrence of complete responsein patients with poor prognosis testicular cancer.