- 作者：Francesca Mazzoni ; Fabiana Letizia Cecere ; Giulia Meoni ; Costanza Giuliani ; Luca Boni ; Andrea Camerini ; Sara Lucchesi ; Francesca Martella ; Domenico Amoroso ; Elisa Lucherini ; Francesca Torricelli ; Francesco Di Costanzo
- 关键词：Non-small-cell lung cancer ; Chemotherapy ; Polymorphisms ; SNPs ; ERCC1 ; RRM1
- 刊名：Lung Cancer
- 出版年：November, 2013
- 年：2013
- 卷：82
- 期：2
- 页码：288-293
- 全文大小：684 K
Objectives
Customized chemotherapy has several advantages: patients are more likely to be treated with the most effective agents and can be spared the toxicity of ineffective drugs. Based on the literature, excision repair cross complementation group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) genes represent predictive biomarkers of response to platinum compound and gemcitabine, in NSCLC.Materials and methods
We had planned a phase II trial (Simon design) to evaluate combination chemotherapy according to single nucleotide polymorphisms (SNPs) of ERCC1 (118T/C and 8092C/A) and RRM1 (鈭?7C/A and 鈭?24T/C) in na茂ve patients affected by advanced NSCLC. ERCC1 and RRM1 SNPs assessment was performed in peripheral blood lymphocytes (PBLs). Combination chemotherapy was selected based on ERCC1 and RRM1 SNPs: we assume that patients with one or two C alleles at position 118 and with one or two A alleles at position 8092 in ERCC1 gene would correspond to Cisplatin non-responder and than with two A alleles at 鈭?7 and two C alleles at 鈭?24 in RRM1 gene to gemcitabine non-responder. Four schedules were provided: cisplatin + gemcitabine, cisplatin + docetaxel, gemcitabine + docetaxel; docetaxel + vinorelbine. Primary endpoint was overall response (ORR) in the intention-to-treat population.
Results
42 patients were enrolled from January 2010 to November 2011; 40 patients received at least 1 cycle of chemotherapy; median age was 66 years (range: 47-72); 36(90%) had stage IV, 4(10%) IIIB; 23(58%) had adenocarcinoma, 14(35%) squamous carcinoma. Twenty-five (62%) patients received treatment A, 3(8%) treatment B, 11(28%) treatment C, 1(23%) treatment D. ORR was 55%, analysis in squamous patients subgroups showed 71.4% ORR. The median follow-up was 19.7 months, PFS was 23 weeks (95% CI = 15-26) and OS was 40.4 weeks (95% CI = 32-55). Treatment was well tolerated.
Conclusion
We observed an increase of ORR in NSCLC patients when they were treated with chemotherapy according to ERCC1 and RRM1 SNPs status.