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

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Abstract
Seventeen patients with ‘poor prognosis’ non-seminomatous testicular cancer were monitored for formation of intrastrand bidentate N 7 -d(ApG)- and N 7 -d(GpG)- diammineplatinum adducts in peripheral blood cell DNA during the course of cisplatin-based chemotheraphy. Adduct values from blood cell DNA samples were compared with disease response data from the same individuals. Patients who received a dose of 40 mg/m 2 cisplatin for 5 days generally formed more adducts than patients receiving 20 mg/m 2 for 5 days, and adduct levels ranged from 0 to approximately 300 amol/μg DNA. Among the individuals who achieved a complete response, the median adduct level was 170 amol/μg DNA and the mean was 162. Among the individuals who achieved a partial response, the median adduct level was 78 amol/ μg DNA and the mean was 83. Comparison of adduct levels between response groups using the Mann-Whitney test gave a two-sided P value of 0.072 (one-sided P value 0.036). Of 11 patients forming high levels of adduct (>140 amol/μg DNA), 10 achieved a complete response; this compares with two complete responders in the group of six patients forming low levels (P = 0.055, two-sided Fisher exact test). We conclude that cisplatin-DNA adduct formation in peripheral blood cell DNA correlates with the occurrence of complete response in patients with poor prognosis testicular cancer.

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