Efficacy of imatinib in aggressive fibromatosis: Results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial Journal Article
| Authors: | 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. |
| Article Title: | Efficacy of imatinib in aggressive fibromatosis: Results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial |
| 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 m2], 200 mg twice daily (BSA = 1.0-1.49 m2), or 100 mg twice daily (BSA < 1.0 m2). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, plateletderived 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. ©2010 AACR. |
| Keywords: | immunohistochemistry; protein kinase b; adolescent; adult; child; human tissue; protein expression; treatment outcome; treatment response; aged; middle aged; young adult; gene mutation; major clinical study; single nucleotide polymorphism; exon; clinical trial; fatigue; neutropenia; doxorubicin; drug dose reduction; drug efficacy; antineoplastic agents; methotrexate; polymerase chain reaction; allele; imatinib; platelet derived growth factor alpha receptor; stem cell factor; dacarbazine; progression free survival; phase 2 clinical trial; drug administration schedule; clinical assessment; dose-response relationship, drug; pyrimidines; vinblastine; rash; sarcoma; prescription; dna; drug mechanism; multicenter study; sulindac; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; clinical evaluation; clinical research; tamoxifen; maximum tolerated dose; piperazines; beta catenin; apc protein; desmoid tumor; transcription factor fkhr; platelet derived growth factor beta receptor; raloxifene; aggressive fibromatosis; kaplan-meier estimate; meloxicam; body surface; fibromatosis; functional disease; fibromatosis, aggressive |
| Journal Title: | Clinical Cancer Research |
| Volume: | 16 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-10-01 |
| Start Page: | 4884 |
| End Page: | 4891 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-10-1177 |
| PUBMED: | 20724445 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus" |
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