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Conference Paper: Correlation of Src activation with response to dasatinib, capecitabine, oxaliplatin, and bevacizumab in advanced solid tumors

TitleCorrelation of Src activation with response to dasatinib, capecitabine, oxaliplatin, and bevacizumab in advanced solid tumors
Authors
Issue Date2013
PublisherLippincott Williams & Wilkins.
Citation
The 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO 2013), Chicago, IL., 31 May-4 June 2013. In Journal of Clinical Oncology, 2013, v. 31 n. 15 suppl., abstract no. 11036 How to Cite?
AbstractBACKGROUND: Src inhibition may augment sensitivity to chemotherapy, but in unselected patients (pts) with advanced solid tumors, src inhibitors have shown limited clinical activity. Biomarkers to predict benefit from src inhibitors in advanced solid tumors are not yet known. METHODS: 22 pts (dose escalation cohort= 12 pts; colorectal cancer [CRC] expansion cohort= 10 pts) were enrolled in a phase I study to determine the safety and tolerability of the src inhibitor dasatinib with capecitabine, oxaliplatin, and bevacizumab (J Clin Oncol 29: 2011 [suppl; abstr 3586]). Src activation (src-a) was assessed in tumors from 16 evaluable pts. Src-a was measured by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded tumor samples using an antibody that selectively recognizes the active conformation of src (clone 28). A GI pathologist who was blinded to pt outcomes graded membranous src-a using a standard semi-quantitative method. The endpoint of this exploratory analysis was objective response rate ([ORR]= PR+CR). 2-sided Fisher’s Exact test was used to evaluate the association between ORR and src-a. RESULTS: Across all tumor types, 8 tumors had no/faint src-a (IHC=0/1); 8 tumors had moderate/strong src-a (IHC 2). Benign colonic epithelium had no src-a (IHC=0). The ORR was 75% (6/8) for pts with moderate/strong src-a versus (vs) 0% (0/8) for pts with no/faint src-a (p =0.007). In the CRC expansion cohort, the ORR was 83% (5/6) for patients with moderate/strong src-a vs 0% (0/2) for pts with no/faint src-a (p=0.107); progression free survival range was 7.9-24.4 months for pts with moderate/strong src-a. CONCLUSIONS: In this small phase I study, src-a is associated with benefit from the combination of dasatinib and oxaliplatin-based chemotherapy. Further evaluation of dasatinib in patients whose tumors demonstrate high levels of src-a may be warranted. Clinical trial information: NCT00920868.
DescriptionThis journal suppl. entitled: 2013 ASCO Annual Meeting Abstracts
Persistent Identifierhttp://hdl.handle.net/10722/195790
ISSN
2015 Impact Factor: 20.982
2015 SCImago Journal Rankings: 9.204

 

DC FieldValueLanguage
dc.contributor.authorStrickler, JHen_US
dc.contributor.authorMcCall, Sen_US
dc.contributor.authorNixon, ABen_US
dc.contributor.authorPang, HMHen_US
dc.contributor.authorRushing, Cen_US
dc.contributor.authorArrowood, Cen_US
dc.contributor.authorHaley, Sen_US
dc.contributor.authorMeadows, Ken_US
dc.contributor.authorHurwitz, Hen_US
dc.date.accessioned2014-03-10T04:53:30Z-
dc.date.available2014-03-10T04:53:30Z-
dc.date.issued2013en_US
dc.identifier.citationThe 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO 2013), Chicago, IL., 31 May-4 June 2013. In Journal of Clinical Oncology, 2013, v. 31 n. 15 suppl., abstract no. 11036en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/195790-
dc.descriptionThis journal suppl. entitled: 2013 ASCO Annual Meeting Abstracts-
dc.description.abstractBACKGROUND: Src inhibition may augment sensitivity to chemotherapy, but in unselected patients (pts) with advanced solid tumors, src inhibitors have shown limited clinical activity. Biomarkers to predict benefit from src inhibitors in advanced solid tumors are not yet known. METHODS: 22 pts (dose escalation cohort= 12 pts; colorectal cancer [CRC] expansion cohort= 10 pts) were enrolled in a phase I study to determine the safety and tolerability of the src inhibitor dasatinib with capecitabine, oxaliplatin, and bevacizumab (J Clin Oncol 29: 2011 [suppl; abstr 3586]). Src activation (src-a) was assessed in tumors from 16 evaluable pts. Src-a was measured by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded tumor samples using an antibody that selectively recognizes the active conformation of src (clone 28). A GI pathologist who was blinded to pt outcomes graded membranous src-a using a standard semi-quantitative method. The endpoint of this exploratory analysis was objective response rate ([ORR]= PR+CR). 2-sided Fisher’s Exact test was used to evaluate the association between ORR and src-a. RESULTS: Across all tumor types, 8 tumors had no/faint src-a (IHC=0/1); 8 tumors had moderate/strong src-a (IHC 2). Benign colonic epithelium had no src-a (IHC=0). The ORR was 75% (6/8) for pts with moderate/strong src-a versus (vs) 0% (0/8) for pts with no/faint src-a (p =0.007). In the CRC expansion cohort, the ORR was 83% (5/6) for patients with moderate/strong src-a vs 0% (0/2) for pts with no/faint src-a (p=0.107); progression free survival range was 7.9-24.4 months for pts with moderate/strong src-a. CONCLUSIONS: In this small phase I study, src-a is associated with benefit from the combination of dasatinib and oxaliplatin-based chemotherapy. Further evaluation of dasatinib in patients whose tumors demonstrate high levels of src-a may be warranted. Clinical trial information: NCT00920868.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins.en_US
dc.relation.ispartofJournal of Clinical Oncologyen_US
dc.titleCorrelation of Src activation with response to dasatinib, capecitabine, oxaliplatin, and bevacizumab in advanced solid tumorsen_US
dc.typeConference_Paperen_US
dc.identifier.emailPang, HMH: herbpang@hku.hken_US
dc.identifier.authorityPang, HMH=rp01857en_US
dc.identifier.volume31en_US
dc.identifier.issue15 suppl. (May 20 Supplement)-
dc.publisher.placeUnited Statesen_US

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