title: A randomized phase II trial of ERCC1 and RRM1 mRNA expression-based chemotherapy versus docetaxel/carboplatin in advanced non-small cell lung cancer.
abstract: OBJECTIVE
  To evaluate whether the selection of first-line chemotherapy based on ERCC1 and RRM1 mRNA expression levels would improve clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Eligible patients were randomly assigned 1:1 to the experimental and control arms; the experimental arm received gemcitabine/carboplatin (GC) if ERCC1 and RRM1 expression was low, gemcitabine/vinorelbine (GV) if ERCC1 was high and RRM1 was low, docetaxel/carboplatin (DC) if ERCC1 was low and RRM1 was high, and docetaxel/vinorelbine (DV) if both were high. In the control arm, patients received DC.
  
  
  RESULTS
  This study was prematurely terminated after the futility analysis of 43 progression-free survival (PFS) events. A total of 55 patients (n = 26 in the experimental arm, n = 29 in the control arm) were evaluable for efficacy and toxicity. Nineteen (73.1%) patients were assigned to receive GC, 0 (0.0%) to GV, 4 (15.4%) to DC, and 3 (11.5%) to DV in the experimental arm. The overall response rates were 42.3 and 48.3% in the experimental and control arms, respectively, which were not statistically different (P = 0.657). The median PFS was 5.2 months in the experimental arm and 5.4 months in the control arm (P = 0.286). The median overall survival was 17.4 months in the experimental arm and 12.6 months in the control arm (P = 0.638). The occurrence of grade 3 or higher neutropenia (69.2 vs. 93.1%, P = 0.035) and febrile neutropenia (3.8 vs. 24.1%, P = 0.054) was more common in the control arm.
  
  
  CONCLUSIONS
  ERCC1 and RRM1 mRNA expression-based chemotherapy did not improve clinical outcomes in advanced NSCLC (NCT01648517).
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Jung
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea.
authors.forename: Choong-Kun
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea.
authors.forename: Jee Hung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea.
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea.
authors.forename: Yong Wha
authors.initials: YW
authors.lastname: Moon
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.affiliation: Division of Medical Oncology and Hematology, Department of Internal Medicine, School of Medicine, Kyunghee University, Seoul, Korea.
authors.forename: Jaeheon
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea.
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea. nobelg@yuhs.ac.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea. cbc1971@yuhs.ac.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012262:Ribonucleoside Diphosphate Reductase; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D043823:Taxoids; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D016190:Carboplatin; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases; D000077235:Vinorelbine; D000093542:Gemcitabine
keywords: Chemotherapy; ERCC1; Non-small cell lung cancer; RRM1; mRNA expression