title: Customized chemotherapy in metastatic non-small cell lung cancer (NSCLC).
abstract: Metastatic non-small cell lung cancer (NSCLC) unfortunately remains a lethal disease, despite recent genetic characterization of subclasses of NSCLC, mainly adenocarcinoma, which has led to the development of targeted therapies that improve progression-free survival (PFS). Ultimately, however, patients fatally relapse. In this review we will focus on the search to improve survival for NSCLC patients deemed to be pan-negative for the common driver alterations susceptible to targeted therapy, above all those with EGFR mutations or ALK, ROS or RET translocations. Other uncommon driver mutations such as HER2 and BRAF mutations should be tested in order to rule out targeted treatment before assigning patients to chemotherapy. Chemotherapy yields short lived response with median survival still less than one year. Customized chemotherapy represents one way to attempt to prolong survival, although to date no prospective randomized customized studies have reported sufficient evidence to support this. In one attempt to demonstrate the role of tailoring chemotherapy, the Spanish Lung Cancer Group (SLCG) phase II customized chemotherapy trial (NCT00883480) showed that RAP80, a component of the BRCA1-A complex, influenced outcome in patients with low BRCA1 expression treated with cisplatin/gemcitabine, and in patients with intermediate/high BRCA1 levels receiving cisplatin/docetaxel or docetaxel alone. We are currently performing a prospective, randomized phase III trial comparing non-customized cisplatin/docetaxel with customized therapy in metastatic NSCLC patients (NCT00617656/GECP-BREC) and a parallel phase II study (ChiCTR-TRC-12001860) is being carried out in China (BREC-China) under the auspices of the SLCG.
authors: Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
authors: Jia
authors: J
authors: Wei
authors: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916 Badalona, Spain ;
authors: Teresa
authors: T
authors: Moran
authors: Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
authors: Zhengyun
authors: Z
authors: Zou
authors: Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
authors: Xiaoping
authors: X
authors: Qian
authors: Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
authors: Lifeng
authors: L
authors: Wang
authors: Hospital General Universitario de Valencia, Av Tres Cruces, s/n, 46014 Valencia, Spain ;
authors: Carlos
authors: C
authors: Camps
authors: Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
authors: Wenjing
authors: W
authors: Hu
authors: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916 Badalona, Spain ;
authors: Imane
authors: I
authors: Chaib
authors: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916 Badalona, Spain ;
authors: Belén
authors: B
authors: Sanchez
authors: Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
authors: Lixia
authors: L
authors: Xu
authors: Breakthrough Cancer Research Unit, Pangaea Biotech S.L, Quiron Dexeus University Hospital, Sabino Arana 5-19, 08028 Barcelona;
authors: Niki
authors: N
authors: Karachaliou
authors: Universidad Alcalá de Henares, Pza. San Diego s/n, 28801 Alcalá de Henares, Madrid, Spain.
authors: María
authors: M
authors: Sanchez-Ronco
authors: Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
authors: Baorui
authors: B
authors: Liu
authors: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916 Badalona, Spain ; ; Breakthrough Cancer Research Unit, Pangaea Biotech S.L, Quiron Dexeus University Hospital, Sabino Arana 5-19, 08028 Barcelona;
authors: Rafael
authors: R
authors: Rosell
keywords: BRCA1; BRCA1 and RAP80 expression customized (BREC); Non-small cell lung cancer; RAP80; RING finger protein 8 (RNF8); customized chemotherapy