Reed E, Ostchega Y, Steinberg S M, Yuspa S H, Young R C, Ozols R F, Poirier M C
Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Res. 1990 Apr 15;50(8):2256-60.
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.
顺铂或卡铂单药化疗可使约30%先前接受过治疗的晚期卵巢癌患者获得缓解。既往研究表明，在接受顺铂或卡铂治疗的卵巢癌患者白细胞DNA中测得的铂-DNA加合物形成程度与疾病反应直接相关（Reed等人，《美国国家科学院院刊》，84: 5024 - 5028，1987）。尚不清楚白细胞DNA中的加合物水平是否独立于该疾病已知的预后变量，或者加合物水平是否与一个更易于监测的已知预后变量平行。在一组接受顺铂或卡铂单药治疗的24例卵巢癌患者中，我们通过单因素分析和多因素分析回顾性评估了疾病反应、白细胞DNA中的铂-DNA加合物与八个预后变量之间的关系。评估的预后变量包括：对先前治疗的反应、卡诺夫斯基状态、当前治疗前的总铂剂量、疾病分期、年龄、治疗开始时的疾病体积、组织学类型和组织学分级。通过单因素分析，加合物水平与疾病反应密切相关（双侧P = 0.0058），与疾病反应次强相关的是卡诺夫斯基状态（P = 0.125）、疾病分期（P = 0.189）、对先前治疗的反应（P = 0.352）、先前的总铂剂量（P = 0.358）和年龄（P = 0.374）。未发现加合物水平与组织学类型或组织学分级之间存在显著关联。此外，当根据研究的周期数（一个周期、两个周期或三个周期）对患者进行分层时，在对治疗有反应的患者中始终观察到较高水平的加合物。我们得出结论，在这一小群接受顺铂或卡铂单药治疗的难治性卵巢癌患者中，白细胞DNA中的加合物水平似乎比其他先前确定的预后变量与疾病反应更密切相关。
