title: Evaluation of platinum-DNA adduct levels relative to known prognostic variables in a cohort of ovarian cancer patients.
abstract: Single-agent chemotherapy with cisplatin or carboplatin can induce remissions in approximately 30% of previously treated patients with advanced stage ovarian cancer. Previous studies have shown that the extent of platinum-DNA adduct formation measured in WBC DNA of ovarian cancer patients treated with cisplatin or carboplatin is directly associated with disease response (Reed et al., Proc. Natl. Acad. Sci. USA, 84: 5024-5028, 1987). It has been unclear whether adduct level in WBC DNA is independent of known prognostic variables in this disease, or whether adduct level parallels a known prognostic variable that can be more easily monitored. In a cohort of 24 ovarian cancer patients treated with single-agent cisplatin or carboplatin, we retrospectively assessed the relationship between disease response, platinum-DNA adducts in WBC DNA, and each of eight prognostic variables by both univariate analysis and multivariate analysis. The prognostic variables evaluated included: response to previous treatment, Karnofsky status, total platinum dose prior to current therapy, stage of disease, age, bulk of disease at initiation of therapy, histological type, and histological grade. By univariate analysis, adduct level was strongly associated with disease response (two-sided P = 0.0058), with the next strongest associations with disease response being held by Karnofsky status (P = 0.125), stage of disease (P = 0.189), response to previous treatment (P = 0.352), total previous platinum dose (P = 0.358), and age (P = 0.374). No significant associations were found between adduct level and histological type or histological grade. Further, when patients were stratified by the number of cycles studied (one cycle, two cycles, or three cycles), higher levels of adduct were consistently seen in those patients responding to therapy. We conclude that, in this small cohort of refractory ovarian cancer patients treated with single-agent cisplatin or carboplatin, adduct level in WBC DNA appears to be more closely related to disease response than other previously identified prognostic variables.
authors.affiliation: Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: E
authors.initials: E
authors.lastname: Reed
authors.forename: Y
authors.initials: Y
authors.lastname: Ostchega
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: S H
authors.initials: SH
authors.lastname: Yuspa
authors.forename: R C
authors.initials: RC
authors.lastname: Young
authors.forename: R F
authors.initials: RF
authors.lastname: Ozols
authors.forename: M C
authors.initials: MC
authors.lastname: Poirier
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin; D002945:Cisplatin / Q000627:therapeutic use*; D015331:Cohort Studies; D004247:DNA / Q000097:blood*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000032:analysis*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010984:Platinum / Q000097:blood*; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010984:Platinum; D004247:DNA; D016190:Carboplatin; D002945:Cisplatin