Kim Hee Seung, Kim Tae Joong, Chung Hyun Hoon, Kim Jae Weon, Kim Byung Gie, Park Noh Hyun, Song Yong Sang, Bae Duk Soo, Kang Soon Beom
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yeongun-Dong Jongno-Gu, Seoul 110-744, Republic of Korea.
J Cancer Res Clin Oncol. 2009 Nov;135(11):1513-20. doi: 10.1007/s00432-009-0598-0. Epub 2009 May 16.
We sought to investigate the efficacy of in vitro extreme drug resistance (EDR) assay for the prediction of drug response, platinum-resistance (progression-free survival, PFS <6 months) and survival in patients with epithelial ovarian cancer (EOC) who received taxane- and platinum-based chemotherapy after surgery.
Between December 2005 and August 2007, 43 patients were enrolled prospectively. They underwent staging laparotomy followed by six or nine cycles of taxane- and platinum-based chemotherapy, and their tumors were submitted for in vitro EDR assay to taxanes (paclitaxel or docetaxel) and platinum compounds (carboplatin or cisplatin).
The rates of EDR to taxanes and platinum compounds were 20.9% (9/43) and 23.3% (10/43). Patients with EDR to platinum compounds showed a lower rate of overall response (60 vs. 100%), a higher rate of platinum-resistance (50 vs. 18.2%) and poor overall survival (OS) (median OS; 29.2 vs. 33.7 months) than those without EDR to platinum compounds (P < 0.05), whereas patients with EDR to taxanes showed poor PFS than those without EDR to taxanes (12.5 vs. 19 months, P < 0.01). Moreover, suboptimal debulking surgery and EDR to taxanes were poor prognostic factors for PFS (adjusted hazard ratio 3.215 and 3.984; 95% confidence interval 1.845-7.895 and 3.814-11.674, respectively) although there was no independent risk factor for poor OS by the multivariate Cox's proportional hazard analysis.
In vitro EDR assay to taxanes and platinum compounds may be helpful for predicting drug response, platinum-resistance and survival in patients with EOC who received taxane- and platinum-based chemotherapy after staging laparotomy.
我们旨在研究体外极端耐药性(EDR)检测对于预测接受手术治疗后接受紫杉烷和铂类化疗的上皮性卵巢癌(EOC)患者的药物反应、铂耐药性(无进展生存期,PFS<6个月)和生存率的有效性。
2005年12月至2007年8月,前瞻性纳入43例患者。他们接受了分期剖腹手术,随后进行了六个或九个周期的紫杉烷和铂类化疗,并将其肿瘤送检进行针对紫杉烷(紫杉醇或多西他赛)和铂类化合物(卡铂或顺铂)的体外EDR检测。
对紫杉烷和铂类化合物的EDR率分别为20.9%(9/43)和23.3%(10/43)。对铂类化合物有EDR的患者与无铂类化合物EDR的患者相比,总缓解率较低(60%对100%),铂耐药率较高(50%对18.2%),总生存期(OS)较差(中位OS;29.2个月对33.7个月)(P<0.05),而对紫杉烷有EDR的患者与无紫杉烷EDR的患者相比,PFS较差(12.5个月对19个月,P<0.01)。此外,减瘤手术不彻底和对紫杉烷有EDR是PFS的不良预后因素(调整后的风险比分别为3.215和3.984;95%置信区间分别为1.845-7.895和3.814-11.674),尽管多因素Cox比例风险分析未发现OS不良的独立危险因素。
针对紫杉烷和铂类化合物的体外EDR检测可能有助于预测接受分期剖腹手术后接受紫杉烷和铂类化疗的EOC患者的药物反应、铂耐药性和生存率。