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 (-37C/A and -524T/C) in naïve 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 -37 and two C alleles at -524 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.
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 (-37C/A and -524T/C) in naïve 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 -37 and two C alleles at -524 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 NSCLCpatients when they were treated with chemotherapy according to ERCC1 and RRM1 SNPs status.
Authors: Ting Deng; Hong Pan; Rubing Han; Dingzhi Huang; Hongli Li; Likun Zhou; Xia Wang; Ming Bai; Xiang Li; Rui Liu; Shaohua Ge; Tao Ning; Le Zhang; Yi Ba Journal: Int J Clin Exp Med Date: 2014-12-15
Authors: Aurélie Mbeutcha; Ilaria Lucca; Vitaly Margulis; Jose A Karam; Christopher G Wood; Michela de Martino; Romain Mathieu; Andrea Haitel; Evanguelos Xylinas; Luis Kluth; Morgan Rouprêt; Pierre I Karakiewicz; Alberto Briganti; Michael Rink; Malte Rieken; Alon Z Weizer; Jay D Raman; Nathalie Rioux-Leclecq; Christian Bolenz; Karim Bensalah; Yair Lotan; Christian Seitz; Mesut Remzi; Shahrokh F Shariat; Tobias Klatte Journal: World J Urol Date: 2015-12-11 Impact factor: 4.226