Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab

Anne M. Schultheis, Georg Lurje, Katrin E. Rhodes, Wu Zhang, Dongyun Yang, Agustin A. Garcia, Robert Morgan, David R Gandara, Sidney A Scudder, Amit Oza, Hal Hirte, Gini Fleming, Lynda Roman, Heinz Josef Lenz

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152 Scopus citations

Abstract

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 33P 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 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). 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.

Original languageEnglish (US)
Pages (from-to)7554-7563
Number of pages10
JournalClinical Cancer Research
Volume14
Issue number22
DOIs
StatePublished - Nov 15 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Schultheis, A. M., Lurje, G., Rhodes, K. E., Zhang, W., Yang, D., Garcia, A. A., Morgan, R., Gandara, D. R., Scudder, S. A., Oza, A., Hirte, H., Fleming, G., Roman, L., & Lenz, H. J. (2008). Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab. Clinical Cancer Research, 14(22), 7554-7563. https://doi.org/10.1158/1078-0432.CCR-08-0351