Two-drug combination may slow deadly thyroid cancer

Volume 2, Issue 1, 2013

Summary

A combination of pazopanib and paclitaxel shows promise in slowing anaplastic thyroid cancer, a rare cancer that is resistant to most therapies.

Keith C. Bible, M.D., Ph.D.

Keith C. Bible, M.D., Ph.D.

A combination of the drugs pazopanib and paclitaxel shows promise in slowing anaplastic thyroid cancer (ATC), according to a Mayo Clinic Cancer Center-led study published in the January 2013 issue of the journal Science Translational Medicine. The two drugs together resulted in greater anticancer activity in anaplastic thyroid cancer than either drug alone, said lead researcher Keith C. Bible, M.D., Ph.D., a Mayo Clinic Cancer Center oncologist.

Anaplastic thyroid cancer is a rare but devastating form of thyroid cancer that typically strikes men and women in their 60s and 70s. This kind of thyroid cancer is very aggressive, with a median survival of only about five months from time of diagnosis. Anaplastic thyroid cancer has historically been found to be resistant to most therapies.

Pazopanib, a kinase inhibitor that interferes with the growth of cancer cells, is already approved by the Food and Drug Administration (FDA) to treat renal cancer tumors. Paclitaxel is an FDA-approved chemotherapy drug that disrupts the machinery involved in cell division.

Mayo Clinic Cancer Center researchers studied anaplastic thyroid cancer cells and tumors in cell culture and in animal models. Human cancer cells were readily killed, and tumors implanted in mice were 50 percent smaller when treated with the pazopanib-paclitaxel combination compared with the response to treatment with either drug alone. Pilot therapy of one patient with metastatic anaplastic thyroid cancer using the combination also resulted in marked tumor shrinkage lasting more than six months. "This was a highly unexpected finding for this type of aggressive tumor, which often can double in size in a matter of days," Dr. Bible said.

In previous studies, pazopanib alone was found to be ineffective in the treatment of anaplastic thyroid cancer. Paclitaxel was added to address the aggressiveness of anaplastic thyroid cancer tumors and bolster anticancer effects. The Cancer Center team investigated how the two drugs might complement each other.

Monitoring cancer cells as they multiplied in time-lapse video under a microscope, researchers noted that the drug combination resulted in abnormal cell division and an increase in cancer cell death. Although pazopanib had not been known to specifically affect cell division, researchers speculated that the drug might have another unrecognized molecular target within cancer cells.

"We ended up learning that pazopanib also happens to inhibit a protein involved in cell division known as Aurora A; this property seems to be involved in producing enhanced effects when pazopanib is combined with paclitaxel," Dr. Bible said. "This finding suggests that the combination may also be useful in treating other cancers, such as breast cancer, in which Aurora A is sometimes found to be present in elevated amounts, as it is in ATC."

The results also prompted an ongoing randomized multicenter clinical trial, led by Mayo Clinic and Memorial Sloan-Kettering Cancer Center and administered through the Radiation Therapy Oncology Group, testing the two-drug combination when added to radiation therapy in the initial treatment of patients with anaplastic thyroid cancer. "This important next step is designed to determine whether the combination of drugs will improve anaplastic thyroid cancer patient survival compared to paclitaxel alone," Dr. Bible said.

Watch a video of Dr. Bible discussing the anaplastic thyroid cancer study.