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


METHODS
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.


CONCLUSIONS
Imatinib may have a role in the management of unresectable or difficult to resect desmoid tumors.
Chugh
Rashmi
R
Department of Internal Medicine, University of Michigan, Ann Arbor, 48109-5843, USA. rashmim@umich.edu
Wathen
J Kyle
JK
Patel
Shreyaskumar R
SR
Maki
Robert G
RG
Meyers
Paul A
PA
Schuetze
Scott M
SM
Priebat
Dennis A
DA
Thomas
Dafydd G
DG
Jacobson
Jon A
JA
Samuels
Brian L
BL
Benjamin
Robert S
RS
Baker
Laurence H
LH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D018222:Desmoid Tumors / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate