title: [Chinese multicenter randomized trial of customized chemotherapy based on BRCA1 (breast cancer susceptibility gene 1)-RAP80 (receptor-associated protein 80) mRNA expression in advanced non-small cell lung cancer (NSCLC) patients].
abstract: Objective:BRCA1 (breast cancer susceptibility gene 1) and RAP80 (receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes. A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression.Methods:Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm. Patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin (Arm 1), those with intermediate/high RAP80 expression and low/intermediate BRCA1expression received docetaxel/cisplatin (Arm 2), and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3). The primary end point was progression-free survival (PFS).Results:226 patients were screened and 124 were randomized in this trial. ORR in the four subgroups was 22.6%, 48.4%, 30.3% and 19.2%, respectively (P=0.08); PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84). The common adverse effects included neutropenia, nausea, anemia and fatigue.Conclusions:No statistically significant difference of ORR, PFS or OS is observed in the experimental arms compared with the control arm. Patients with low RAP80 mRNA levels have a trend of better survival and higher response rate to gemcitabine/cisplatin chemotherapy.
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: X P
authors.initials: XP
authors.lastname: Qian
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Zou
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: L F
authors.initials: LF
authors.lastname: Wang
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: L X
authors.initials: LX
authors.lastname: Yu
authors.affiliation: Department of Oncology, Suqian General Hospital, Suqian 223800, China.
authors.forename: C W
authors.initials: CW
authors.lastname: You
authors.affiliation: Department of Respiratory Medicine, Jinlin Hospital, Nanjing 210002, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Oncology, Taizhou General Hospital, Taizhou 225300, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Lu
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: W J
authors.initials: WJ
authors.lastname: Hu
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Respiratory Medicine, Northern Jiangsu People's Hospital, Yangzhou 225001, China.
authors.forename: X X
authors.initials: XX
authors.lastname: Xu
authors.affiliation: Department of Oncology, Huaian General Hospital, Huaian 223300, China.
authors.forename: X F
authors.initials: XF
authors.lastname: Chen
authors.affiliation: Department of Oncology, Affiliated Hospital to Zhengzhou University, Zhengzhou 450052 , China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Oncology, Yixing General Hospital, Yixing 214200, China.
authors.forename: Q F
authors.initials: QF
authors.lastname: Wu
authors.affiliation: Department of Oncology, Yixing General Hospital, Yixing 214200, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Maanshan General Hospital, Maanshan 243000, China.
authors.forename: F L
authors.initials: FL
authors.lastname: Zhang
authors.affiliation: The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
authors.forename: B R
authors.initials: BR
authors.lastname: Liu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D056488:Histone Chaperones; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009687:Nuclear Proteins / Q000378:metabolism*; D012333:RNA, Messenger; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D043823:Taxoids; C466234:UIMC1 protein, human; D003841:Deoxycytidine; D000077143:Docetaxel; D002945:Cisplatin; D000093542:Gemcitabine