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 language | English (US) |
|---|---|
| Pages (from-to) | 7554-7563 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 14 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 15 2008 |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab. / Schultheis, Anne M.; Lurje, Georg; Rhodes, Katrin E.; Zhang, Wu; Yang, Dongyun; Garcia, Agustin A.; Morgan, Robert; Gandara, David R; Scudder, Sidney A; Oza, Amit; Hirte, Hal; Fleming, Gini; Roman, Lynda; Lenz, Heinz Josef.
In: Clinical Cancer Research, Vol. 14, No. 22, 15.11.2008, p. 7554-7563.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab
AU - Schultheis, Anne M.
AU - Lurje, Georg
AU - Rhodes, Katrin E.
AU - Zhang, Wu
AU - Yang, Dongyun
AU - Garcia, Agustin A.
AU - Morgan, Robert
AU - Gandara, David R
AU - Scudder, Sidney A
AU - Oza, Amit
AU - Hirte, Hal
AU - Fleming, Gini
AU - Roman, Lynda
AU - Lenz, Heinz Josef
PY - 2008/11/15
Y1 - 2008/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=58149346076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149346076&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-0351
DO - 10.1158/1078-0432.CCR-08-0351
M3 - Article
C2 - 19010874
AN - SCOPUS:58149346076
VL - 14
SP - 7554
EP - 7563
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 22
ER -