Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab.
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.
Schultheis
Anne M
AM
University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
Lurje
Georg
G
Rhodes
Katrin E
KE
Zhang
Wu
W
Yang
Dongyun
D
Garcia
Agustin A
AA
Morgan
Robert
R
Gandara
David
D
Scudder
Sidney
S
Oza
Amit
A
Hirte
Hal
H
Fleming
Gini
G
Roman
Lynda
L
Lenz
Heinz-Josef
HJ
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003520:Cyclophosphamide