title: Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy.
abstract: We sought to find blood-based biomarkers that can be used to predict efficacy in advanced non-small cell lung cancer patients treated with bevacizumab plus chemotherapy. Blood was collected before treatment and after 6 weeks of therapy from patients who were participating in a phase 4 trial. Plasma vascular endothelial growth factor (VEGF) levels were evaluated by ELISA. A total of eight single nucleotide polymorphisms in four candidate genes were analyzed by PCR and sequencing. A total of 45 patients enrolled in a clinical trial at Guangdong General Hospital between August 2007 and March 2008 were used as subjects. The median survival times of OS was 25.6 and 13.4 months in the low and high groups, respectively, when the median posttreatment plasma VEGF level (46.63 pg/ml) was used as the cut-off point (P = 0.0284). Patients carrying the AA genotype at the -6C > A polymorphism in laminin 5 (LN5) were more likely to exhibit reduced hemoglobin compared with patients carrying the CA/CC genotype (OR = 8.364, χ(2) = 5.34, P = 0.021). Similar associations were found at the -89A > G and -260C > A polymorphisms in LN5. Patients with the CC genotype at the -6C > A polymorphism in LN5 had an increased risk of neutropenia than those with the CA/AA genotype (OR = 4.444, χ(2) = 5.116, P = 0.030). Our results show improved survival in patients with lower posttreatment plasma VEGF levels treated with bevacizumab plus chemotherapy; thus, the posttreatment plasma VEGF level may be a promising biomarker to predict clinical benefit early in the course of therapy. Polymorphisms in LN5 were associated with a reduced level of hemoglobin and neutropenia.
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, Peoples Republic of China.
authors.forename: She-Juan
authors.initials: SJ
authors.lastname: An
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Huang
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Jian-Guang
authors.initials: JG
authors.lastname: Chen
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yan
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Jin-Ji
authors.initials: JJ
authors.lastname: Yang
authors.forename: Xue-Ning
authors.initials: XN
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xu-Chao
authors.initials: XC
authors.lastname: Zhang
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000097794:Kalinin
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015815:Cell Adhesion Molecules; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000097794:Kalinin; C467484:VEGFA protein, human