17-allylaminogeldanamycin in advanced medullary and differentiated thyroid carcinoma.

5582 Background: 17-allylaminogeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic that destabilizes heat shock protein 90 (HSP-90) complexes, including RET and multiple cancer-involved proteins. 17-AAG promotes apoptosis and down-regulates RET in thyroid cancer cell lines. Methods: Two one-stage phase II clinical trials were conducted to assess whether the 1 year (yr) treatment failure-free (TFF) rate with 17-AAG was at least 20% in patients (pts) with locoregionally advanced/metastatic MTC or in pts with DTC. Eligibility criteria included: measurable disease by RECIST criteria; ECOG status 0-2; adequate laboratory values, no significant cardiac disease, and no active CNS metastases. 17-AAG dosing was 220 mg/m2 IV over 2 hours (days 1, 4, 8, and 11 of a 21-day cycle). Treatment was discontinued for disease progression, unacceptable toxicity or refusal. If 4 or more of 33 pts in a given cohort remained on treatment at 1 yr, 17-AAG would be considered promising in that cohort. Both trials were disc...