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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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1158/1078-0432.CCR-08-0351 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2586993</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>19010874</sourcerecordid><originalsourceid>FETCH-LOGICAL-c473t-debf04a429ca5a631b0f95e5d6f3d70faa5dcee79d84df9f2caea289088c8793</originalsourceid><addsrcrecordid>eNpVkEuLFDEUhQtRnHH0JyjZuHBRY56dZCNo4QsGWobeh9upm6lIvUiqe2h_venpdtRVDuQ758JXVa8ZvWZMmfeMalNTKfh109zWtGSh2JPqkimla8FX6mnJf5iL6kXOPyllklH5vLpgljJqtLys-h9TfximNHcxD5nA2JKmj2P00JP1bvHTgCSO5Bb9LiUcF7LeQ4owkgZGj4lsEsKCLbmPS0eag--nuZvy3MEQW3yY-4R78PHXboDty-pZgD7jq_N7VW2-fN403-qb9dfvzceb2kstlrrFbaASJLceFKwE29JgFap2FUSraQBQrUfUtjWyDTZwDwjcWGqMN9qKq-rDaXbebQcs6Lgk6N2c4gDp4CaI7v-fMXbubto7rszKWlEG1GnApynnhOGxy6g72ndHs-5o1hX7jpZc7Jfem38P_22ddRfg7RmAXAyHVCTG_MhxajUT9jj07sR18a67jwmdf9CdMCMk3zkmHedOKyXFb1NMoBc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>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</creator><creatorcontrib>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</creatorcontrib><description>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 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.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-08-0351</identifier><identifier>PMID: 19010874</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>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</subject><ispartof>Clinical cancer research, 2008-11, Vol.14 (22), p.7554-7563</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-debf04a429ca5a631b0f95e5d6f3d70faa5dcee79d84df9f2caea289088c8793</citedby><cites>FETCH-LOGICAL-c473t-debf04a429ca5a631b0f95e5d6f3d70faa5dcee79d84df9f2caea289088c8793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20971391$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19010874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SCHULTHEIS, Anne M</creatorcontrib><creatorcontrib>LURJE, Georg</creatorcontrib><creatorcontrib>HIRTE, Hal</creatorcontrib><creatorcontrib>FLEMING, Gini</creatorcontrib><creatorcontrib>ROMAN, Lynda</creatorcontrib><creatorcontrib>LENZ, Heinz-Josef</creatorcontrib><creatorcontrib>RHODES, Katrin E</creatorcontrib><creatorcontrib>WU ZHANG</creatorcontrib><creatorcontrib>DONGYUN YANG</creatorcontrib><creatorcontrib>GARCIA, Agustin A</creatorcontrib><creatorcontrib>MORGAN, Robert</creatorcontrib><creatorcontrib>GANDARA, David</creatorcontrib><creatorcontrib>SCUDDER, Sidney</creatorcontrib><creatorcontrib>OZA, Amit</creatorcontrib><title>Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>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 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.</description><subject>Angiogenesis</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bevacizumab</subject><subject>Biological and medical sciences</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Disease-Free Survival</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Medical sciences</subject><subject>Metronomic Chemotherapy</subject><subject>Ovarian Cancer</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - mortality</subject><subject>Pharmacology. Drug treatments</subject><subject>Pilot Projects</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEuLFDEUhQtRnHH0JyjZuHBRY56dZCNo4QsGWobeh9upm6lIvUiqe2h_venpdtRVDuQ758JXVa8ZvWZMmfeMalNTKfh109zWtGSh2JPqkimla8FX6mnJf5iL6kXOPyllklH5vLpgljJqtLys-h9TfximNHcxD5nA2JKmj2P00JP1bvHTgCSO5Bb9LiUcF7LeQ4owkgZGj4lsEsKCLbmPS0eag--nuZvy3MEQW3yY-4R78PHXboDty-pZgD7jq_N7VW2-fN403-qb9dfvzceb2kstlrrFbaASJLceFKwE29JgFap2FUSraQBQrUfUtjWyDTZwDwjcWGqMN9qKq-rDaXbebQcs6Lgk6N2c4gDp4CaI7v-fMXbubto7rszKWlEG1GnApynnhOGxy6g72ndHs-5o1hX7jpZc7Jfem38P_22ddRfg7RmAXAyHVCTG_MhxajUT9jj07sR18a67jwmdf9CdMCMk3zkmHedOKyXFb1NMoBc</recordid><startdate>20081115</startdate><enddate>20081115</enddate><creator>SCHULTHEIS, Anne M</creator><creator>LURJE, Georg</creator><creator>HIRTE, Hal</creator><creator>FLEMING, Gini</creator><creator>ROMAN, Lynda</creator><creator>LENZ, Heinz-Josef</creator><creator>RHODES, Katrin E</creator><creator>WU ZHANG</creator><creator>DONGYUN YANG</creator><creator>GARCIA, Agustin A</creator><creator>MORGAN, Robert</creator><creator>GANDARA, David</creator><creator>SCUDDER, Sidney</creator><creator>OZA, Amit</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20081115</creationdate><title>Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-debf04a429ca5a631b0f95e5d6f3d70faa5dcee79d84df9f2caea289088c8793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Angiogenesis</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bevacizumab</topic><topic>Biological and medical sciences</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Disease-Free Survival</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Medical sciences</topic><topic>Metronomic Chemotherapy</topic><topic>Ovarian Cancer</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - mortality</topic><topic>Pharmacology. Drug treatments</topic><topic>Pilot Projects</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Restriction Fragment Length</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHULTHEIS, Anne M</creatorcontrib><creatorcontrib>LURJE, Georg</creatorcontrib><creatorcontrib>HIRTE, Hal</creatorcontrib><creatorcontrib>FLEMING, Gini</creatorcontrib><creatorcontrib>ROMAN, Lynda</creatorcontrib><creatorcontrib>LENZ, Heinz-Josef</creatorcontrib><creatorcontrib>RHODES, Katrin E</creatorcontrib><creatorcontrib>WU ZHANG</creatorcontrib><creatorcontrib>DONGYUN YANG</creatorcontrib><creatorcontrib>GARCIA, Agustin A</creatorcontrib><creatorcontrib>MORGAN, Robert</creatorcontrib><creatorcontrib>GANDARA, David</creatorcontrib><creatorcontrib>SCUDDER, Sidney</creatorcontrib><creatorcontrib>OZA, Amit</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SCHULTHEIS, Anne M</au><au>LURJE, Georg</au><au>HIRTE, Hal</au><au>FLEMING, Gini</au><au>ROMAN, Lynda</au><au>LENZ, Heinz-Josef</au><au>RHODES, Katrin E</au><au>WU ZHANG</au><au>DONGYUN YANG</au><au>GARCIA, Agustin A</au><au>MORGAN, Robert</au><au>GANDARA, David</au><au>SCUDDER, Sidney</au><au>OZA, Amit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2008-11-15</date><risdate>2008</risdate><volume>14</volume><issue>22</issue><spage>7554</spage><epage>7563</epage><pages>7554-7563</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><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 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 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.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>19010874</pmid><doi>10.1158/1078-0432.CCR-08-0351</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2008-11, Vol.14 (22), p.7554-7563 |
| issn | 1078-0432 1557-3265 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| 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 |
| title | Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab |
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