Clinical Efficacy and Predictive Molecular Markers of Neoadjuvant Gemcitabine and Pemetrexed in Resectable Non-small Cell Lung Cancer

被引:98
作者
Bepler, Gerold [1 ]
Sommers, K. Eric [1 ]
Cantor, Alan [1 ]
Li, Xueli [1 ]
Sharma, Anupama [1 ]
Williams, Charles [1 ]
Chiappori, Alberto [1 ]
Haura, Eric [1 ]
Antonia, Scott [1 ]
Tanvetyanon, Tawee [1 ]
Simon, George [1 ]
Obasaju, Coleman [2 ]
Robinson, Lary A. [1 ]
机构
[1] H Lee Moffitt Canc Ctr & Res Inst, Program & Dept Thorac Oncol, Tampa, FL 33612 USA
[2] Eli Lilly & Co, Indianapolis, IN 46285 USA
关键词
Gemcitabine; Pemetrexed; Ribonucleotide reductase; Thymidylate synthase; Non-small cell lung cancer;
D O I
10.1097/JTO.0b013e3181874936
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: A trial of neoadjuvant gemcitabine and pemetrexed (GP) chemotherapy in patients with resectable non-small cell lung cancer was conducted. The goal was to achieve a disease response rate of 50% and to determine if the expression levels of genes associated with GP metabolism are predictive of response. Methods: Patients had staging with a computed tomography scan, whole body F-18 fluorodeoxyglucose positron emission tomography, and mediastinoscopy. Four biweekly cycles of GP were given. Patients were restaged, and those with resectable stage IB-III disease had thoracotomy. Fresh frozen tumor specimens were collected before and after chemotherapy and the mRNA levels of 14 target genes determined by real-time reverse transcription polymerase chain reaction. Results: Fifty-two patients started therapy. The radiographic disease response rate was 35% (95% confidence interval 21.7-49.6%), and the progression rate was 6%. Forty-six patients had a thoracotomy. The complete tumor resection rate was 77% (40/52). There were no perioperative deaths or deaths related to chemotherapy. Tumor response to chemotherapy was inversely cot-related with the level of expression of RRM1 (p < 0.001; regulatory subunit of ribonucleotide reductase) and TS (p = 0.006; thymidylate synthase); i.e., the reduction in tumor size was greater in those with low levels of expression. Conclusions: Neoadjuvant GP is well tolerated and produces an objective response rate of 35%. Tumoral RRM1 and TS mRNA levels are predictive of disease response and should be considered as parameters for treatment selection in future trials with this regimen.
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收藏
页码:1112 / 1118
页数:7
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