Clinical Application
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
Wei Jia, Qian Xiaoping, Zou Zhengyun, Wang Lifeng, Yu Lixia, You Chuanwen, Song Yong, Lu Huiyu, Hu Wenjing, Yan Jing, Xu Xingxiang, Chen Xiaofei, Li Xingya, Wu Qinfang, Zhou Yan, Zhang Feiling, Liu Baorui
Published 2016-11-23
Cite as Chin J Oncol, 2016,38(11): 868-873. DOI: 10.3760/cma.j.issn.0253-3766.2016.11.013
Abstract
ObjectiveBRCA1 (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.
MethodsAdvanced 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).
Results226 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.
ConclusionsNo 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.
Key words:
Carcinoma, non-small-cell lung; Drug therapy; Breast cancer susceptibility gene 1; Receptor-associated protein 80; Treatment outcome
Contributor Information
Wei Jia
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
Qian Xiaoping
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
Zou Zhengyun
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
Wang Lifeng
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
Yu Lixia
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
You Chuanwen
Department of Oncology, Suqian General Hospital, Suqian 223800, China
Song Yong
Department of Respiratory Medicine, Jinlin Hospital, Nanjing 210002, China
Lu Huiyu
Department of Oncology, Taizhou General Hospital, Taizhou 225300, China
Hu Wenjing
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
Yan Jing
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
Xu Xingxiang
Department of Respiratory Medicine, Northern Jiangsu People′s Hospital, Yangzhou 225001, China
Chen Xiaofei
Department of Oncology, Huaian General Hospital, Huaian 223300, China
Li Xingya
Department of Oncology, Affiliated Hospital to Zhengzhou University, Zhengzhou 450052 , China
Wu Qinfang
Department of Oncology, Yixing General Hospital, Yixing 214200, China
Zhou Yan
Department of Oncology, Yixing General Hospital, Yixing 214200, China
Zhang Feiling
Department of Oncology, Maanshan General Hospital, Maanshan 243000, China
Liu Baorui
The Comprehensive Cancer Center, Affiliated Drum Tower Hospital to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China