Efficacy of imatinib in aggressive fibromatosis: Results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial

Chugh, R., Wathen, J. K., Patel, S. R., Maki, R. G., Meyers, P. A., Schuetze, S. M., Priebat, D. A., Thomas, D. G., Jacobson, J. A., Samuels, B. L., Benjamin, R. S., Baker, L. H., Sarcoma Alliance for Research through, Collaboration (October 2010) Efficacy of imatinib in aggressive fibromatosis: Results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial. Clin Cancer Res, 16 (19). pp. 4884-91. ISSN 1078-0432 (Print)1078-0432 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/20724445
DOI: 10.1158/1078-0432.CCR-10-1177


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 (PDGFRalpha), PDGFRbeta, AKT, PTEN, FKHR, and beta-catenin. Tumor DNA was analyzed for PDGFRalpha 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.

Item Type: Paper
Uncontrolled Keywords: Adolescent Adult Aged Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use Benzamides Child Dose-Response Relationship, Drug Drug Administration Schedule Female Fibromatosis, Aggressive/diagnosis/*drug therapy Humans Imatinib Mesylate Immunohistochemistry Kaplan-Meier Estimate Male Maximum Tolerated Dose Middle Aged Piperazines/administration & dosage/adverse effects/*therapeutic use Pyrimidines/administration & dosage/adverse effects/*therapeutic use Treatment Outcome Young Adult
Subjects: diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 1 October 2010
Date Deposited: 25 Oct 2016 18:46
Last Modified: 25 Oct 2016 18:46
Related URLs:
URI: https://repository.cshl.edu/id/eprint/33706

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving