Relationship between patient response in ovarian and breast cancer and platinum drug-DNA adduct formation.
Nucleated blood cell DNA samples from ovarian (n = 27) and breast (n = 25) cancer patients receiving either cis-diamminedichloroplatinum II (cisplatin) and/or diamminecyclobutanecarboxylatoplatinum II were examined for the presence of platinum drug bound to DNA during several cycles of therapy. Platinum-DNA adducts were quantitated by cisplatin-DNA enzyme-linked immunosorbent assay (ELISA) and atomic absorbance spectroscopy, techniques that measure either a fraction of the intrastrand cis-diammineplatinum-d(ApG) and -d(GpG) adducts (ELISA) or the total platinum bound to DNA (atomic absorbance spectroscopy), respectively. For either the complete study, or for samples obtained during the early cycles, individuals with progressive disease had severalfold lower overall cisplatin-DNA ELISA-measurable adduct levels than the individuals with more favorable clinical responses (complete response, partial response, or stable disease), who were grouped together and termed nonprogressive disease. In the case of the ovarian cancer patients, who experienced a 59% rate of complete and partial response, the correlation of high adduct values with disease response was statistically significant by the Wilcoxon rank-sum test (P = 0.028). In contrast, the breast cancer patients achieved only an 11.5% rate of complete and partial response, and the correlation of high adduct formation with disease response was not statistically significant. Levels of total DNA-bound platinum, measured by atomic absorbance spectroscopy, showed no correlation with disease response for either cancer by any analysis. The study supports previous observations demonstrating a consistent correlation between high cisplatin-DNA ELISA measurements and positive clinical outcome in ovarian cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Gupta-Burt
S
S
Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Shamkhani
H
H
Reed
E
E
Tarone
R E
RE
Allegra
C J
CJ
Pai
L H
LH
Poirier
M C
MC
D001681:Biological Assay; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D004247:DNA / Q000187:drug effects*; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D012074:Remission Induction; D013054:Spectrophotometry, Atomic
D004247:DNA; D016190:Carboplatin; D002945:Cisplatin