Prevalence of in vitro extreme chemotherapy resistance in resected nonsmall-cell lung cancer
Prevalence of in vitro extreme chemotherapy resistance in resected nonsmall-cell lung cancer
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DOI：
10.1016/j.athoracsur.2005.08.037
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发表时间：
2006-02-01
影响因子：
4.6
通讯作者：
Parker, RJ
中科院分区：
文献类型：
--
作者：
d'Amato, TA;Landreneau, RJ;Parker, RJ
背景。最近的临床试验表明，辅助化疗为完全切除的非小细胞肺癌（NSCLC）患者提供了生存优势，但许多患者接受化疗没有任何益处。肿瘤对抗肿瘤药物的体外耐药可高度预测某些癌症对化疗的临床无反应；然而，对人类非小细胞肺癌肿瘤极端化疗耐药性的流行程度知之甚少。化疗耐药试验可能是预测治疗失败、选择替代药物和避免不必要的化疗毒性的一种方法。本研究描述了非小细胞肺癌患者肿瘤培养中体外化疗耐药的流行情况。在增殖试验中，共培养了3042个NSCLC标本，并测试了它们对卡铂、顺铂、阿霉素、依托泊苷、吉西他滨、纳韦滨、紫杉醇、泰索替雷或拓扑替康的耐药性。采用h -3-胸腺嘧啶摄取法测定细胞生长抑制率，分别测定极端耐药、中等耐药和低耐药情况。1565例NSCLC培养物中有1056例（68%）对卡铂有极端耐药或中度耐药，2227例中有1409例（63%）对顺铂有耐药，1471例中有1101例（75%）对阿霉素有耐药，2505例中有1581例（63%）对莱泊苷有耐药，823例中有594例（72%）对吉西他滨有耐药，1444例中有603例（42%），1706例中有689例（40%）对紫杉醇有耐药，521例中有273例（52%）对紫杉醇有耐药，896例中有280例（31%）对拓扑替康有耐药。化疗耐药在非小细胞肺癌临床细胞培养中普遍存在。这可能解释了经验性辅助化疗的小生存率。在制定非小细胞肺癌切除术辅助治疗计划时，应考虑使用活肿瘤培养物进行体外化疗耐药试验。未来的试验比较患者在定制和经验辅助治疗后的生存率似乎是合理的。
Background. Recent clinical trials suggest that adjuvant chemotherapy provides a survival advantage for patients with completely resected nonsmall-cell lung cancer (NSCLC) yet many patients receive chemotherapy without benefit. Tumor in vitro resistance to antineoplastic agents is highly predictive of clinical unresponsiveness to chemotherapy for some cancers; however, little is known of the prevalence of extreme chemotherapy drug resistance for human NSCLC tumors. Chemoresistance testing may be a way to predict treatment failure, choose alternative agents, and to avoid unnecessary chemotherapy toxicity. This study describes the prevalence of in vitro chemotherapy resistance in NSCLC patient tumor cultures.Methods. A total of 3,042 NSCLC specimens were cultured in a proliferation assay and tested for resistance to carboplatin, cisplatin, doxorubicin, etoposide, gemcitabine, navelbine, paclitaxel, taxotere, or topotecan. The percentage of cell-growth inhibition measured by H-3-Thymidine uptake was used to determine extreme drug resistance, intermediate drug resistance, or low drug resistance.Results. Extreme drug resistance or intermediate drug resistance to carboplatin was found in 1,056 of 1,565 NSCLC cultures (68%), to cisplatin in 1,409 of 2,227 (63%), to doxorubicin in 1,101 of 1,471 (75%), to etoposide in 1,581 of 2,505 (63%), to gemcitabine in 594 of 823 (72%), to navelbine in 603 of 1,444 (42%), to paclitaxel in 689 of 1,706 (40%), to taxotere in 273 of 521 (52%), and to topotecan in 280 of 896 (31%).Conclusions. Chemotherapy resistance is prevalent among NSCLC clinical cell cultures. This may account for the small survival seen with empiric adjuvant chemotherapy. The use of viable tumor culture for in vitro chemoresistance testing should be considered when formulating a plan of adjuvant therapy for resected NSCLC. Future trials comparing patient survival after tailored versus empiric adjuvant therapy appear justified.