title: Circulating tumor cells: application as a biomarker for molecular characterization and predictor of survival in an all-comer solid tumor phase I clinical study.
abstract: OBJECTIVE
  Clinical development of cancer drugs has a low success rate. Prognostic and predictive biomarkers using minimally invasive approaches hold promise for increasing the probability of success by enabling disease characterization, patient selection and early detection of drug treatment effect. Enumeration and molecular characterization of circulating tumor cells (CTC) may address some of these needs, and thus were evaluated for utility in a Phase I solid tumor clinical study.
  
  
  METHODS
  Blood samples for CTC analysis were obtained from 24 cancer patients in a multi-center all-comer Phase I study of MEDI-575, a novel anti-PDGFRα antibody. Samples were taken at screening and analyzed for enumeration of CTC using the CellSearch(®) platform and for molecular characterization using a novel quantitative RT-PCR assay.
  
  
  RESULTS
  Fifty-nine percent of the patients showed at least 1 CTC per 7.5 ml of blood at baseline. Progression-free survival (PFS) and overall survival (OS) of patients with 0 CTCs at baseline were longer than PFS and Os for patients with 1-3 and >3 CTCs (8.8 versus 1.4 and 1.3 months PFS, P = 0.02; 9.0 vs 7.4 and 3.5 months OS, P = 0.20, respectively). Patients with 0 CTC showed a greater percentage of stable disease than the other 2 groups with 1-3 and >3 CTCs (57% vs 29% and 0%). The multimarker qRT-PCR method detected CTC in 40% of the patients, and 80% of these patients were positive for pre-selected drug target genes.
  
  
  CONCLUSIONS
  CTC enumeration of patients in an all-comer study is feasible and may allow for patient stratification for PFS and Os to evaluate the clinical response of investigational agents. Gene expression profiling of isolated CTC may provide a means for molecular characterization of selected tumor targets.
authors.affiliation: Department of Translational Sciences, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Bao
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Burke
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Huang
authors.forename: Xiaoru
authors.initials: X
authors.lastname: Chen
authors.forename: Philip Z
authors.initials: PZ
authors.lastname: Brohawn
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yao
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lechleider
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sikorski
authors.forename: Manuela
authors.initials: M
authors.lastname: Buzoianu
authors.forename: Jianliang
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Shi
authors.forename: Laura K
authors.initials: LK
authors.lastname: Richman
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Lavallee
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating; D011336:Probability; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor