Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Thorac Cardiovasc Surg. 2010 Aug;140(2):352-5. doi: 10.1016/j.jtcvs.2009.11.072.
Optimizing the multimodality treatment of malignant pleural mesothelioma depends on many factors including an adequate chemotherapeutic response. Currently, chemotherapy regimens for patients with mesothelioma are empirically selected. In vitro chemotherapy resistance in human mesothelioma has not been reported. Our goal was to determine the prevalence of drug resistance in a large sample of malignant pleural mesothelioma using a commercially available assay.
Tumors specimens (n = 203) were cultured for analysis of chemoresistance using the extreme drug resistance assay. Evaluable results were obtained in 168 (168/203 = 83%) specimens. Each specimen was tested with 3 drugs: cisplatin, gemcitabine, and vinorelbine. Drug resistance was characterized as low, intermediate, or extreme. Median age was 64 years (30-85 years). Forty-four (26%) patients received neoadjuvant chemotherapy before sampling and testing. The distribution of histopathologic cell types was epithelial (103; 61%), mixed (57; 34%), and sarcomatoid (8; 5%).
A significant proportion of tumors had extreme/intermediate drug resistance to cisplatin (27%), gemcitabine (31%), or vinorelbine (59%). Nineteen tumors (11%) had extreme/intermediate resistance to all 3 drugs. Resistance (extreme/intermediate) to cisplatin was more prevalent in epithelial tumors than in nonepithelial (33% vs 18%; P = .0394). No significant differences in chemoresistance were found in tumors of patients who had received neoadjuvant chemotherapy compared with those who had not.
The feasibility of performing off-site in vitro drug resistance assays on resected malignant mesothelioma specimens is reported. A significant proportion of mesothelioma tumors exhibited extreme/intermediate resistance to cisplatin, gemcitabine, or vinorelbine.
恶性胸膜间皮瘤的多模态治疗的优化取决于许多因素，包括充分的化疗反应。目前，间皮瘤患者的化疗方案是经验性选择的。尚未报道人类间皮瘤的体外化疗耐药性。我们的目标是使用市售的测定法在大量恶性胸膜间皮瘤标本中确定耐药性的发生率。
使用极端耐药测定法培养肿瘤标本（n = 203）进行化疗耐药性分析。在 168 个（168/203 = 83%）标本中获得了可评估的结果。每个标本均用 3 种药物进行测试：顺铂、吉西他滨和长春瑞滨。耐药性特征为低、中和极端。中位年龄为 64 岁（30-85 岁）。44 例（26%）患者在取样和检测前接受了新辅助化疗。组织病理学细胞类型的分布为上皮型（103；61%）、混合型（57；34%）和肉瘤样型（8；5%）。
相当一部分肿瘤对顺铂（27%）、吉西他滨（31%）或长春瑞滨（59%）具有明显的耐药性。19 例（11%）肿瘤对 3 种药物均具有耐药性（中度/高度耐药）。上皮型肿瘤的耐药性（中度/高度耐药）比非上皮型肿瘤更常见（33%比 18%；P =.0394）。与未接受新辅助化疗的患者相比，接受新辅助化疗的患者的肿瘤化疗耐药性无明显差异。
报道了在切除的恶性间皮瘤标本上进行场外体外药物耐药测定的可行性。相当一部分间皮瘤肿瘤对顺铂、吉西他滨或长春瑞滨表现出中度/高度耐药。
