The measurement of cisplatin-DNA adduct levels in testicular cancer patients.
Seventeen patients with 'poor prognosis' non-seminomatous testicular cancer were monitored for formation of intrastrand bidentate N7-d(ApG)- and N7-d(GpG)-diammineplatinum adducts in peripheral blood cell DNA during the course of cisplatin-based chemotherapy. 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/m2 cisplatin for 5 days generally formed more adducts than patients receiving 20 mg/m2 for 5 days, and adduct levels ranged from 0 to approximately 300 amol/micrograms DNA. Among the individuals who achieved a complete response, the median adduct level was 170 amol/micrograms DNA and the mean was 162. Among the individuals who achieved a partial response, the median adduct level was 78 amol/micrograms 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 (greater than 140 amol/micrograms DNA), 10 achieved a complete response; this compares with two complete responders in the group of six patients forming low levels (less than 100 amol/micrograms DNA) of adduct (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.
Reed
E
E
Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.
Ozols
R F
RF
Tarone
R
R
Yuspa
S H
SH
Poirier
M C
MC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage / Q000097:blood*; D004247:DNA / Q000097:blood*; D018736:DNA Adducts; D004273:DNA, Neoplasm / Q000097:blood*; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008297:Male; D011379:Prognosis; D013736:Testicular Neoplasms / Q000097:blood* / Q000188:drug therapy; D014747:Vinblastine / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D018736:DNA Adducts; D004273:DNA, Neoplasm; C057270:cisplatin-DNA adduct; D001761:Bleomycin; D014747:Vinblastine; D005047:Etoposide; D004247:DNA; D002945:Cisplatin