Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab

Purpose: 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. Experimental Design: Seventy recurrent/metastatic epithelial ovarian cancer patients were enro...

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Bibliographic Details
Published in:Clinical cancer research 2008-11, Vol.14 (22), p.7554-7563
Main Authors: SCHULTHEIS, Anne M, LURJE, Georg, HIRTE, Hal, FLEMING, Gini, ROMAN, Lynda, LENZ, Heinz-Josef, RHODES, Katrin E, WU ZHANG, DONGYUN YANG, GARCIA, Agustin A, MORGAN, Robert, GANDARA, David, SCUDDER, Sidney, OZA, Amit
Format: Article
Language:English
Subjects:
Angiogenesis
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal, Humanized
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bevacizumab
Biological and medical sciences
Cyclophosphamide - administration & dosage
Disease-Free Survival
Drug Resistance, Neoplasm - genetics
Female
Female genital diseases
Gynecology. Andrology. Obstetrics
Humans
Kaplan-Meier Estimate
Medical sciences
Metronomic Chemotherapy
Ovarian Cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - genetics
Ovarian Neoplasms - mortality
Pharmacology. Drug treatments
Pilot Projects
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Tumors
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Summary:Purpose: 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. Experimental Design: 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 33 P γATP-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 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). Conclusion: 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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-08-0351