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

被引：176

作者：

Chugh, Rashmi ^{[1
]}

Wathen, J. Kyle ^{[4
]}

Patel, Shreyaskumar R. ^{[4
]}

Maki, Robert G. ^{[5
]}

Meyers, Paul A. ^{[5
]}

Schuetze, Scott M. ^{[1
]}

Priebat, Dennis A. ^{[6
]}

Thomas, Dafydd G. ^{[2
]}

Jacobson, Jon A. ^{[3
]}

Samuels, Brian L. ^{[7
]}

Benjamin, Robert S. ^{[4
]}

Baker, Laurence H. ^{[1
]}

机构：

[1] Univ Michigan, Div Hematol Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA

[4] Univ Texas MD Anderson Canc Ctr, Div Oncol, Houston, TX 77030 USA

[5] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[6] Washington Canc Inst, Washington, DC USA

[7] Kootenai Canc Ctr, Coeur Dalene, ID USA

来源：

CLINICAL CANCER RESEARCH | 2010年 / 16卷 / 19期

关键词：

FAMILIAL ADENOMATOUS POLYPOSIS; DESMOID TUMORS; GARDNERS-SYNDROME; MANAGEMENT; THERAPY; CHEMOTHERAPY; METHOTREXATE; VINBLASTINE; SUBTYPES; BREAST;

D O I：

10.1158/1078-0432.CCR-10-1177

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 alpha (PDGFR alpha), PDGFR beta, AKT, PTEN, FKHR, and beta-catenin. Tumor DNA was analyzed for PDGFR alpha 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. (C) 2010 AACR.

引用

页码：4884 / 4891

页数：8

共 32 条

[1] THE MANAGEMENT OF DESMOID TUMORS [J].