New metastatic medullary thyroid cancer treatment options

Our researchers are waging war on every cancer, no matter how many -- or how few -- are impacted.

Take progressive, metastatic medullary thyroid cancer: Only tens to a few hundred Americans were diagnosed with it in 2012. Yet MD Anderson has a team dedicated to this cancer, and its research has resulted in a new treatment that stalls tumor progression and even shrinks tumors in some patients.

"Rare cancers get intense focus here, so they aren't rare to us," says Steven Sherman, M.D., chair of Endocrine Neoplasia and Hormonal Disorders. "Each year, we treat between 175 and 350 medullary thyroid cancer (MTC) patients, many of whom have progressive, metastatic disease."

Although thyroid cancers tend to be slow growing, those with progressive, metastatic MTC face different odds. This often fatal disease had no approved treatments until 2011. A second therapy was approved by the Food and Drug Administration (FDA) in November 2012.

MD Anderson played a key role in the development of both treatments.

Step one started in Phase I clinical trials
Like many of today's cancer breakthroughs, the most recent drug for progressive, metastatic MTC -- known as Cabozantinib -- grew out of our increasing understanding of cancer genetics and treatments developed to target specific genetic abnormalities.

"Once several common abnormalities were identified, we collaborated with our Phase I clinical trials program to try to find an experimental drug that targets one or more of them," Sherman explains.

They found one called XL184, which became Cabozantinib.

"We have one patient who achieved 50% tumor reduction, which he's maintained since 2006," says Forlisa Nauling, a Phase I Program research nurse supervisor who worked with all the patients on the trial from 2005 until earlier this year.

That same patient helped the pharmaceutical company discover something about the drug it manufactured. Researchers from our Phase I Program wondered if XL184 affected the RET gene mutation in addition to its other listed inhibitory properties.

When asked, the manufacturer said it hadn't run tests on that particular gene. When it did, it discovered the drug did inhibit RET mutations, which are common in progressive, metastatic MTC patients.

Given the response of several patients, more participated in the study. The response was so encouraging that the drug was allowed to skip the next step and went directly into the last stage of testing.

Medullary thyroid cancer treatment for those who need it most
If cancer metastasizes, it's never a good thing. But some patients whose medullary thyroid cancer spreads can continue to remain stable for long periods of time. The cancer may spread to the liver, for example, and then stop growing or spreading for many years.

There's a subset of people, however, whose MTC metastasizes more aggressively.

"Progressive, metastatic MTC is far more deadly, and we didn't really have any effective treatments for it until now," says Sherman,who spearheaded all stages of the research that led to the FDA's approval of Cabozantinib in November 2012.

When the drug was first tested in our Phase I Program, it had to be mixed into a drink that patients said tasted awful.

"Our patients were so hopeful about the drug that most stuck with it despite the taste," Nauling says. "After about two years, the manufacturer produced it in capsule form, which was a huge benefit for patients."

Patients who took the drug lived an average of 11.2 months without tumor growth, compared to an average of four months for patients who didn't take the drug. In addition, 27% of those who took the drug had reductions in tumor size lasting an average of nearly 15 months, while patients who didn't take the drug saw no reduction."

The genetic revolution has transformed how we practice medicine," Sherman says. "We used to see medullary thyroid patients about once a year for disease management. We didn't see many progressive patients because there really wasn't anything we could offer them. Now, we're a major referral clinic, and we can give them treatment and hope."

A longer version of this article originally appeared in Messenger, MD Anderson's bimonthly publication for employees.