Phase II trial evaluating imatinib (I) in patients (pts) with anaplastic thyroid carcinoma (ATC)

Abstract

6057 Background: There is no standard treatment for ATC. Response to doxorubicin ranges between 5–22%; median survival ranges between 3–6 months. Affymetrix gene chip showed PDGFR overexpression in ATC. In p53 mutated/deficient ATC cell lines, c-Abl is overexpressed, and selective inhibition of c-Abl resulted in cytostatic effect. (I) inhibits tyrosine kinase activity of Bcr-Abl and PDGF. We hypothesize that ATC that overexpress PDGFR or Abl will respond to (I). Methods: Pts ≥ 18 years old with histologically confirmed ATC, overexpressing PDGFR or c-Abl by immunohistochemistry who had measurable disease were eligible. Pts must have Zubrod performance status ≤ 1, and adequate hepatic and renal function. Prior chemotherapy, chemoradiation, radiation therapy, or surgery must have been completed at least 28 days prior to registration. (I) was administered at 400mg orally twice daily without drug holiday. Response to treatment was assessed after every 8 weeks. Pts with complete response (CR)/partial responses (PR)/stable disease (SD) were treated until disease progression. The study was terminated early due to poor accrual. Results: From February 2004 to May 2007, eleven pts from our institution were enrolled and were started on (I) (6 men; 5 women) with a median age of 63 years (ranges 53–80). At baseline, 4/11 pts (36%) had locoregional disease, 5/11 pts (45%) had distant metastases, and 2/11 pts (18%) had both. Nine pts had prior chemoradiation, and 7 pts had thyroidectomy. Out of 11 pts, 8 were evaluable for response; 3 were excluded for lack of follow up radiological evaluation. The overall responses at 8 weeks were CR 0/8; PR 2/8 (25%); SD 4/8 (50%); and PD 2/8 (25%). The median time to follow up was 26 months (ranges 23–30 months). The estimate of 6-month progression free survival was 27% (95% CI, 7–54%). The estimate of 6-month overall survival was 46% (95% CI, 17–71%). The most common G3 toxicity was lymphopenia in 45%; other G3 toxicities included edema (27%), anemia (18%), and hyponatremia (18%). There was no G4 or higher or treatment related death. Conclusions: (I) appears to have activity in advanced ATC and is well tolerated. Due to difficulty of accruing pts with a rare malignancy at a single institution, investigation of (I) in ATC may be warranted in a multi-institution setting. No significant financial relationships to disclose.