Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
Gynecol Oncol. 2017 Nov;147(2):426-432. doi: 10.1016/j.ygyno.2017.08.018. Epub 2017 Aug 19.
Management of epithelial ovarian cancer (EOC) could use serial measurements of invasive circulating tumor cells (iCTCs) for monitoring therapeutic response and early detection of disease progression/recurrence. Goals of this study are to develop an iCTC drug resistance (CDR) assay and to evaluate clinical significance of patient-derived, cultured iCTCs in selecting available therapies.
The CDR assay using Taxol-Carboplatin and eight other EOC drugs at the concentration used for patients was performed. Blood was donated by six patients before primary Taxol-Carboplatin chemotherapy, one recurrent patient, six patients during and after their course of chemotherapy, and two patients with benign disease for procedure control. CDR score above and below 100 indicates sensitivity and resistance, respectively, to that drug.
Five of six pre-therapy samples had >20 iCTCs/>111 CDR for Taxol-Carboplatin sensitivity, and one had 40 iCTCs/23 CDR for resistance. The recurrent sample had 58 iCTCs/5 CDR for resistance. Four of six post-therapy patients had iCTCs decreased to 0/>153 CDR indicating sensitivity, while two patients had >45 iCTCs/<85 CDR indicating resistance. The patients' treatment history and follow-up confirmed that patients were in response or remission when iCTCs were sensitive to Taxol-Carboplatin, and patients were in relapse or recurrence when iCTCs were resistant to Taxol-Carboplatin.
Further investigation on the CDR assay is warranted to examine its use in selecting drugs before treating a patient.
上皮性卵巢癌（EOC）的治疗管理可通过连续测量侵袭性循环肿瘤细胞（iCTC）来监测治疗反应并早期发现疾病进展/复发。本研究的目的是开发一种 iCTC 耐药（CDR）测定法，并评估源自患者的培养 iCTC 在选择可用治疗方法中的临床意义。
使用紫杉醇-卡铂和其他 8 种 EOC 药物进行 CDR 测定，药物浓度与患者所用药物相同。在初次紫杉醇-卡铂化疗前、1 例复发患者、化疗期间和化疗后 6 例患者以及 2 例良性疾病患者献血。CDR 评分高于和低于 100 分别表示对该药物的敏感性和耐药性。
6 例治疗前样本中有 5 例紫杉醇-卡铂敏感性的 iCTC/>111 CDR 超过 20，1 例 iCTC/23 CDR 为耐药性。复发样本中 iCTC/5 CDR 为耐药性，为 58。6 例治疗后患者中有 4 例 iCTC 减少至 0/>153 CDR，表明敏感性，而 2 例患者 iCTC/<85 CDR 表明耐药性。患者的治疗史和随访证实，当 iCTC 对紫杉醇-卡铂敏感时，患者处于缓解或缓解状态，而当 iCTC 对紫杉醇-卡铂耐药时，患者处于复发或复发状态。
需要进一步研究 CDR 测定法，以检查其在治疗患者之前选择药物的用途。
