title: The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib: A Prisma-Compliant Systematic Review and Meta-Analysis.
abstract: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21-0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11-0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinib with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78-1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34-1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07-0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01-0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined to detect an RR of 0.38 for neutropenia, and 78.03% for an RR of 0.32 for leukopenia. The present meta-analysis suggested that erlotinib could decrease the incidence of neutropenia and leukopenia in patients with advanced NSCLC undergoing erlotinib regardless of whether combined with CT or not. The subgroup analysis revealed that erlotinib combine with CT did not affect the incidence; however, erlotinib alone could significantly decrease the incidence of neutropenia and leukopenia compared with CT alone.
authors.affiliation: From the Department of Oncology, Affiliated Hospital of Zunyi Medical University (JGZ, LC,YZ,YJB, HM); Center for Translational Medicine, Zunyi Medical University, Zunyi (JGZ, HM); Graduate College (XT); School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin (XT); Department of Science and Education, First People's Hospital of Changde City, Changde (QZ); Department of Pharmacology (YL); and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China (YL).
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Tian
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Bai
authors.forename: Hu
authors.initials: H
authors.lastname: Ma
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride