von Heideman Anne, Tholander Bengt, Grundmark Birgitta, Cajander Stefan, Gerdin Eva, Holm Leif, Axelsson Agneta, Rosenberg Per, Mahteme Haile, Daniel Erika, Larsson Rolf, Nygren Peter
Department of Radiology, Oncology and Radiation Science, Uppsala University , Uppsala , Sweden.
Acta Oncol. 2014 Feb;53(2):242-50. doi: 10.3109/0284186X.2013.794956. Epub 2013 May 29.
A number of chemotherapeutic drugs are active in epithelial ovarian cancer (EOC) but so far choice of drugs for treatment is mostly empirically based. Testing of drug activity in tumour cells from patients might provide a rationale for a more individualised approach for drug selection.
Sensitivity of EOC to chemotherapeutic drugs was analysed in 125 tumour samples from 112 patients using a short-term primary culture assay based on the concept of total cell kill. Sensitivity was related to tumour histology, treatment status and clinical tumour response.
For most EOC standard drugs serous high grade and clear cell EOC were the most sensitive subtypes and the mucinous tumours the most resistant subtype. Docetaxel, however, tended to show the opposite pattern. Samples from previously treated patients tended to be more resistant than those from treatment naïve patients. The activity of cisplatin correlated with that of other drugs with the exception of docetaxel. Tumour samples from two sites in the same patient at the same occasion showed similar cisplatin sensitivity in contrast to samples taken at different occasions. Samples from patients responding in the clinic to treatment were more sensitive to most drugs than samples from non-responding patients. At the individual patient level, drug sensitivity in vitro compared with clinical response showed sensitivities and specificities in the 83-100% and 55-83% ranges, respectively.
Assessment of EOC tumour cell drug sensitivity in vitro provides clinically relevant and potentially useful information for the optimisation of drug treatment.
多种化疗药物对上皮性卵巢癌（EOC）有活性，但迄今为止，治疗药物的选择大多基于经验。检测患者肿瘤细胞中的药物活性可能为更个体化的药物选择方法提供理论依据。
基于全细胞杀伤概念，采用短期原代培养试验，分析了112例患者的125份肿瘤样本中EOC对化疗药物的敏感性。敏感性与肿瘤组织学、治疗状态和临床肿瘤反应相关。
对于大多数EOC标准药物，浆液性高级别和透明细胞EOC是最敏感的亚型，黏液性肿瘤是最耐药的亚型。然而，多西他赛的表现往往相反。先前接受过治疗的患者的样本往往比未接受过治疗的患者的样本更耐药。除多西他赛外，顺铂的活性与其他药物的活性相关。同一患者在同一时间从两个部位采集的肿瘤样本显示出相似的顺铂敏感性，而不同时间采集的样本则不同。临床上对治疗有反应的患者的样本比无反应患者的样本对大多数药物更敏感。在个体患者水平上，体外药物敏感性与临床反应相比，敏感性和特异性分别在83%-100%和55%-83%范围内。
体外评估EOC肿瘤细胞药物敏感性可为优化药物治疗提供临床相关且可能有用的信息。
