title: Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab.
abstract: OBJECTIVE
  This study was designed to evaluate the associations between angiogenesis gene polymorphisms and clinical outcome in ovarian cancer patients treated with low-dose cyclophosphamide and bevacizumab.
  
  
  METHODS
  Seventy recurrent/metastatic epithelial ovarian cancer patients were enrolled in a phase II clinical trial. Genomic DNA was available from 53 blood samples. Polymorphisms were analyzed using the PCR-RFLP protocol. A 5' end 33P gammaATP-labeled PCR protocol was used to analyze dinucleotide repeats.
  
  
  RESULTS
  Patients genotyped A/A or A/T for the IL-8 T-251A gene polymorphism had a statistically significant lower response rate (19%; 0%) than those homozygous T/T (50%; P = 0.006, Fisher's exact test). Patients carrying a minimum one C allele (C/C; C/T) of the CXCR2 C+785T polymorphism showed a median progression-free survival (PFS) of 7.4 months compared with the PFS of 3.7 months for those homozygous T/T (P = 0.026, log-rank test). Patients with the VEGF C+936T polymorphism C/T genotype had a longer median PFS of 11.8 months, compared with those with the C/C and T/T genotype, which had median PFS of 5.5 months and 3.2 months, respectively (P = 0.061, log-rank test). Patients carrying both AM 3'end alleles < 14 CA repeats had the shortest median PFS of 3.4 months; patients with at least one allele > 14 repeats or both alleles > 14 repeats showed a median PFS of 6.4 months and 7.2 months, respectively (P = 0.008, log-rank test).
  
  
  CONCLUSIONS
  Our data suggest that the IL-8 A-251T polymorphism may be a molecular predictor of response to bevacizumab-based chemotherapy. The CXCR2 C+785T, VEGF C+936T single nucleotide polymorphisms and the AM 3' dinucleotide repeat polymorphisms may be molecular markers for PFS in ovarian cancer patients.
authors.affiliation: University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Schultheis
authors.forename: Georg
authors.initials: G
authors.lastname: Lurje
authors.forename: Katrin E
authors.initials: KE
authors.lastname: Rhodes
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.forename: Dongyun
authors.initials: D
authors.lastname: Yang
authors.forename: Agustin A
authors.initials: AA
authors.lastname: Garcia
authors.forename: Robert
authors.initials: R
authors.lastname: Morgan
authors.forename: David
authors.initials: D
authors.lastname: Gandara
authors.forename: Sidney
authors.initials: S
authors.lastname: Scudder
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
authors.forename: Hal
authors.initials: H
authors.lastname: Hirte
authors.forename: Gini
authors.initials: G
authors.lastname: Fleming
authors.forename: Lynda
authors.initials: L
authors.lastname: Roman
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003520:Cyclophosphamide