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New Drug for Patients with Advanced Thyroid Cancer
Untitled Document
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.
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