In vitro chemoresponse in metachronous pairs of gyneclologic cancers.

Gynecologic oncology research and practice Pub Date : 2014-12-06 eCollection Date: 2014-01-01 DOI:10.1186/2053-6844-1-7
Heather J Dalton, James Fiorica, Candace K McClure, Rodney P Rocconi, Fernando O Recio, John L Levocchio, Matthew O Burrell, Bradley J Monk
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引用次数: 1

Abstract

Background: While most gynecologic cancers respond to first-line cytotoxic chemotherapy, treatment of recurrent disease is frequently associated with acquired drug resistance. In order to find an in vitro surrogate of this clinical phenomenon, a tumor chemoresponse assay was studied.

Methods/materials: Patients who had tissue submitted for repeated chemoresponse testing were identified through a retrospective search. Sixty-three patients met inclusion criteria (chemoresponse testing completed at primary diagnosis and upon recurrence of disease and assays completed ≥90 days apart). The Wilcoxon signed-rank test was used to compare chemoresponse, represented as a response index (RI), between primary and recurrent measurements. In a secondary analysis, response was categorized and coded as Responsive = 3, Intermediately Responsive = 2 and Non-Responsive = 1, and the paired t-test was used to compare chemoresponse between primary and recurrent measurement.

Results: Median time between primary and recurrent tumor testing was 309 days (IQR 208-422). Drugs tested included carboplatin, cisplatin, docetaxel, doxorubicin, gemcitabine, paclitaxel, topotecan, and combination carboplatin/gemcitabine and carboplatin/paclitaxel. There were no differences in chemoresponse between primary and recurrent measurement when chemoresponse was represented by RI scores; although a trend toward increased resistance to paclitaxel upon recurrence was noted. When chemoresponse was analyzed as a continuous variable corresponding to categorized response, a significant shift toward increased resistance to paclitaxel at recurrence, and a marginally significant trend toward increased resistance to carboplatin at recurrence, were observed.

Conclusions: We observed a trend toward increased chemoresistance at recurrence for paclitaxel, and a marginally significant trend toward increased chemoresistance to carboplatin, but no change in chemoresponsiveness between primary diagnosis and recurrence of disease for other common chemotherapy drugs, including common second-line agents such as doxorubicin, gemcitabine, and topotecan.

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异时性妇科肿瘤的体外化学反应。
背景:虽然大多数妇科癌症对一线细胞毒性化疗有反应,但复发性疾病的治疗往往与获得性耐药有关。为了寻找这种临床现象的体外替代物,研究了肿瘤化学反应试验。方法/材料:通过回顾性检索确定组织进行重复化学反应试验的患者。63例患者符合纳入标准(在初次诊断和疾病复发时完成化学反应试验,试验间隔≥90天完成)。Wilcoxon符号秩检验用于比较化学反应,用反应指数(RI)表示,在初次和反复测量之间。在二次分析中,反应被分类并编码为反应= 3,中间反应= 2和无反应= 1,配对t检验用于比较初次测量和反复测量之间的化学反应。结果:原发和复发肿瘤检测之间的中位时间为309天(IQR 208-422)。试验药物包括卡铂、顺铂、多西紫杉醇、阿霉素、吉西他滨、紫杉醇、拓扑替康以及卡铂/吉西他滨和卡铂/紫杉醇联合用药。当化学反应用RI评分表示时,初次测量和复发测量之间的化学反应没有差异;虽然有复发后紫杉醇耐药增加的趋势。当化学反应作为一个连续变量与分类反应相对应时,观察到复发时紫杉醇耐药增加的显著转变,复发时卡铂耐药增加的略微显著趋势。结论:我们观察到紫杉醇复发时化疗耐药增加的趋势,卡铂化疗耐药增加的趋势略微显著,但其他常见化疗药物(包括常见的二线药物,如阿霉素、吉西他滨和拓扑替康)的初始诊断和疾病复发之间的化疗反应性没有变化。
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