Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mol Cancer Ther. 2012 Jun;11(6):1221-5. doi: 10.1158/1535-7163.MCT-11-0864. Epub 2012 Apr 5.
Low levels of human copper transporter 1 (hCtr1) mRNA are associated with a shorter progression-free survival after platinum-based therapy. Pretreatment with a copper-lowering agent such as trientine enhanced hCtr1-mediated platinum uptake. Therefore, we conducted a pilot study (NCT01178112) of carboplatin and trientine with the goal of resensitizing patients with advanced cancer to platinum chemotherapy. This case report reviews the outcomes of 5 patients with platinum-resistant high-grade epithelial ovarian cancer enrolled on the study to date. Overall, they tolerated treatment well. Severe adverse events that occurred in 2 patients were myelosuppression, notably anemia requiring transfusion. Dose-limiting toxicity was not observed within the first 28 days (cycle 1). After 2 cycles of therapy, partial remission was achieved in 1 patient (10+ months), stable disease in 3 patients (2, 3.5+, and 5 months, respectively), and 1 patient had progressive disease. These cases provide preliminary clinical evidence that the role of decreasing copper levels in reversing platinum resistance merits additional clinical investigation. Evaluation of this novel strategy is warranted in larger studies to assess the efficacy of this approach for treating platinum-resistant advanced epithelial ovarian cancer in patients with high copper levels.
人类铜转运蛋白 1 (hCtr1) mRNA 水平低与铂类治疗后无进展生存期缩短相关。用三乙膦酸等降低铜的药物预处理可增强 hCtr1 介导的铂摄取。因此，我们进行了一项卡铂和三乙膦酸的试验研究（NCT01178112），目的是使晚期癌症患者对铂类化疗重新敏感。本病例报告回顾了迄今为止在该研究中入组的 5 例铂耐药高级上皮性卵巢癌患者的结局。总体而言，他们对治疗耐受良好。2 例患者发生严重不良事件，即骨髓抑制，尤其是需要输血的贫血。在第 28 天（第 1 周期）内未观察到剂量限制毒性。在 2 个周期的治疗后，1 例患者达到部分缓解（10+个月），3 例患者病情稳定（分别为 2、3.5+和 5 个月），1 例患者疾病进展。这些病例提供了初步的临床证据，表明降低铜水平在逆转铂耐药方面的作用值得进一步的临床研究。需要在更大的研究中评估这种新策略，以评估这种方法在治疗高铜水平的铂耐药晚期上皮性卵巢癌患者中的疗效。
