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New Drug for Patients with Advanced Thyroid Cancer

Name of the Trial

Phase II Study of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Patients With Inoperable Locoregionally Advanced or Metastatic Medullary or Differentiated Thyroid Carcinoma (MAYO-MC0476). See the protocol summary.

Principal Investigators

Dr. Jeffrey Moley, Washington University (St. Louis), and Dr. Robert Smallridge, Mayo Clinic Cancer Center.

Why This Trial Is Important

Most thyroid gland cancers, including follicular and papillary carcinomas, are well differentiated, slow growing, and highly treatable, often by administering radioactive iodine131 both before and after surgery to remove the thyroid. However, some of these differentiated tumors eventually stop taking up iodine, start behaving aggressively, and metastasize. Medullary thyroid cancers (MTC) arise from a different type of thyroid cell and are generally more aggressive. Many patients with MTC will see their cancer return and metastasize after initial treatment.

Surgery is the only curative treatment for most patients with iodine-resistant differentiated thyroid cancer or MTC. Some patients, however, have tumors that cannot be surgically removed (unresectable), and, in other patients, cancer cells have spread to lymph nodes in the neck or to distant sites, such as the lungs, liver, or bones. No effective treatment has been found for these groups of patients, and new treatment options are needed.

In this phase II trial, researchers are studying the effects of treatment with 17-AAG, an antitumor antibiotic drug that targets a protein called heat shock protein 90 (HSP90), in such patients. Many of the proteins implicated in cancer development need HSP90, a member of a class of proteins called molecular chaperones, to help them achieve their correct functional shape and cellular location. Cancer cells often contain higher levels of HSP90 than normal cells, helping them to grow uncontrollably. In laboratory experiments with MTC, papillary and follicular thyroid carcinomas, and other cancer types, 17-AAG has proven effective in inhibiting cancer cell growth by interfering with the chaperone function of HSP90, which leads, in turn, to the degradation of cellular proteins that promote uncontrolled growth.

"While most thyroid cancers are very slow-growing and survival rates can be good at 15 years or longer, this trial is for that subset of patients with aggressively metastatic disease," said Dr. Moley. "These patients face a difficult challenge, and there haven't been many trials mounted to address their plight."

For More Information

See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The call is toll free and confidential.

  • Posted: November 18, 2008