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Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma Alliance for Research through Collaboration (SARC) Trial

Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma... Purpose: Aggressive fibromatoses (AF; desmoid tumors) are rare clonal neoplastic proliferations of connective tissues that can be locally aggressive despite wide surgical resection and/or radiation therapy. The Sarcoma Alliance for Research through Collaboration (SARC) initiated a prospective phase II trial to investigate the outcome of patients treated with imatinib, a multiple tyrosine kinase inhibitor, in patients with AF, or 1 of 10 sarcoma subtypes. Here, we report specifically on the outcome of patients with AF as well as evaluations undertaken to examine the mechanism of imatinib. Experimental Design: Patients ≥10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg twice daily body surface area (BSA) ≥ 1.5 m 2 , 200 mg twice daily (BSA = 1.0-1.49 m 2 ), or 100 mg twice daily (BSA < 1.0 m 2 ). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, platelet-derived growth factor receptor α (PDGFRα), PDGFRβ, AKT, PTEN, FKHR, and β-catenin. Tumor DNA was analyzed for PDGFRα exon 18 and APC mutations by allelic discrimination PCR. Results: Fifty-one patients were enrolled. The median number of prior regimens was 1. Kaplan-Meier estimates of 2- and 4-month progression-free survival rates were 94% and 88%, respectively, and 1-year progression-free survival was 66%. Objective response rate was 6% (3 of 51). Expression and polymorphisms of target proteins were identified in tissue samples, but no significant correlation with outcome was observed using the samples available. Conclusion: Imatinib may have a role in the management of unresectable or difficult to resect desmoid tumors. Clin Cancer Res; 16(19); 4884–91. ©2010 AACR. Received May 20, 2010. Revision received August 5, 2010. Accepted August 9, 2010. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Cancer Research American Association of Cancer Research

Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma Alliance for Research through Collaboration (SARC) Trial

Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma Alliance for Research through Collaboration (SARC) Trial

Clinical Cancer Research , Volume 16 (19): 4884 – Oct 1, 2010

Abstract

Purpose: Aggressive fibromatoses (AF; desmoid tumors) are rare clonal neoplastic proliferations of connective tissues that can be locally aggressive despite wide surgical resection and/or radiation therapy. The Sarcoma Alliance for Research through Collaboration (SARC) initiated a prospective phase II trial to investigate the outcome of patients treated with imatinib, a multiple tyrosine kinase inhibitor, in patients with AF, or 1 of 10 sarcoma subtypes. Here, we report specifically on the outcome of patients with AF as well as evaluations undertaken to examine the mechanism of imatinib. Experimental Design: Patients ≥10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg twice daily body surface area (BSA) ≥ 1.5 m 2 , 200 mg twice daily (BSA = 1.0-1.49 m 2 ), or 100 mg twice daily (BSA < 1.0 m 2 ). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, platelet-derived growth factor receptor α (PDGFRα), PDGFRβ, AKT, PTEN, FKHR, and β-catenin. Tumor DNA was analyzed for PDGFRα exon 18 and APC mutations by allelic discrimination PCR. Results: Fifty-one patients were enrolled. The median number of prior regimens was 1. Kaplan-Meier estimates of 2- and 4-month progression-free survival rates were 94% and 88%, respectively, and 1-year progression-free survival was 66%. Objective response rate was 6% (3 of 51). Expression and polymorphisms of target proteins were identified in tissue samples, but no significant correlation with outcome was observed using the samples available. Conclusion: Imatinib may have a role in the management of unresectable or difficult to resect desmoid tumors. Clin Cancer Res; 16(19); 4884–91. ©2010 AACR. Received May 20, 2010. Revision received August 5, 2010. Accepted August 9, 2010.

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References (30)

Publisher
American Association of Cancer Research
Copyright
Copyright © 2010 American Association for Cancer Research
ISSN
1078-0432
eISSN
1557-3265
DOI
10.1158/1078-0432.CCR-10-1177
pmid
20724445
Publisher site
See Article on Publisher Site

Abstract

Purpose: Aggressive fibromatoses (AF; desmoid tumors) are rare clonal neoplastic proliferations of connective tissues that can be locally aggressive despite wide surgical resection and/or radiation therapy. The Sarcoma Alliance for Research through Collaboration (SARC) initiated a prospective phase II trial to investigate the outcome of patients treated with imatinib, a multiple tyrosine kinase inhibitor, in patients with AF, or 1 of 10 sarcoma subtypes. Here, we report specifically on the outcome of patients with AF as well as evaluations undertaken to examine the mechanism of imatinib. Experimental Design: Patients ≥10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg twice daily body surface area (BSA) ≥ 1.5 m 2 , 200 mg twice daily (BSA = 1.0-1.49 m 2 ), or 100 mg twice daily (BSA < 1.0 m 2 ). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, platelet-derived growth factor receptor α (PDGFRα), PDGFRβ, AKT, PTEN, FKHR, and β-catenin. Tumor DNA was analyzed for PDGFRα exon 18 and APC mutations by allelic discrimination PCR. Results: Fifty-one patients were enrolled. The median number of prior regimens was 1. Kaplan-Meier estimates of 2- and 4-month progression-free survival rates were 94% and 88%, respectively, and 1-year progression-free survival was 66%. Objective response rate was 6% (3 of 51). Expression and polymorphisms of target proteins were identified in tissue samples, but no significant correlation with outcome was observed using the samples available. Conclusion: Imatinib may have a role in the management of unresectable or difficult to resect desmoid tumors. Clin Cancer Res; 16(19); 4884–91. ©2010 AACR. Received May 20, 2010. Revision received August 5, 2010. Accepted August 9, 2010.

Journal

Clinical Cancer ResearchAmerican Association of Cancer Research

Published: Oct 1, 2010

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