What the FDA's Approval of Azedra Means for Those Who Have or Will Get Neuroendocrine Cancer

Lab researcher

Neuroendocrine cancers are rare; less than 3,000 new cases are reported in the United States each year. This pales in comparison to cancers of the breast and brain, which can see upwards of 300,000 new cases annually.

Because they impact fewer people, neuroendocrine cancers often receive less support and attention, leaving patients who have these cancers with few options for treatment and survival. Daniel A. Pryma, MD, an associate professor of Radiology and Radiation Oncology and Chief of Nuclear Medicine and Clinical Molecular Imaging at Penn’s Perelman School of Medicine, wanted to change that.

In 2009, two years after his arrival at Penn Medicine, Dr. Pryma and a team of researchers in Penn Medicine’s Abramson Cancer Center launched a multi-center trial to test the efficacy of Azedra, a radiotherapy drug that treats malignant, recurrent or unresectable forms of certain neuroendocrine cancers.

"It's a very rare disease and there hadn't been a lot of controlled trials performed in this area. So, there was a big challenge to do a trial," he said.

Recently, the U.S. Food and Drug Administration (FDA) approved Azedra as the first ever non-surgical treatment for rare neuroendocrine cancers, pheochromocytoma and paraganglioma. The approval was based largely on the results of the Penn-led trial involving 68 patients who benefitted from receiving at least one therapeutic dose of Azedra.

“We’ve had patients come from all over the country to be a part of this trial. We had one patient, an older lady from a very rural part of the country, who had been given a standard chemotherapy regimen that wouldn’t really work for this disease. Her oncologists had never treated anyone with this cancer, so they were sort of just trying things and her cancer was sort of just growing and not responding to any treatment,” Dr. Pryma recalled.

“Then, after her first treatment with this drug, her cancer started to shrink. So, even though it’s a small trial, it’s a very important trial for the patients living with this disease.”

Living with Neuroendocrine Cancer

Neuroendocrine tumors, pheochromocytoma and paraganglioma, are formed in and around the adrenal glands. These tumors release hormones that are responsible for creating a fight-or-flight response in humans. 

People living with neuroendocrine cancers often find themselves stuck in fight-or-flight mode, and they may experience extremely high blood pressure and heart rates, simultaneously and at random. Because hormone levels are so high, some people experience cardiac arrhythmia or even cardiac arrest—a significant cause of death in many neuroendocrine cancer patients.

“I’ve had patients who will be sound asleep, and they’ll roll over and leap out of bed as if they’re on fire,” Dr. Pryma explained. “It’s like being in a car accident; they have sudden and extreme surges of adrenaline; their blood pressure shoots up to 220 over 10; they find themselves constantly on edge.”

While it is a very rare disease, the symptoms are common in many other illnesses. So, many patients have a significant delay in diagnosis. This affects the accuracy of both diagnosis and survival estimates.

According to Dr. Pryma, neuroendocrine cancer patients have a 50 percent chance of surviving five years after their diagnosis, but life expectancy can vary based on the time of diagnosis and the types of treatments these patients receive. Some patients can live for a very long time without disease progression and others see swift metastasis and decline. Still, other people go undiagnosed.

“There are a lot of patients who we never know had the disease because it’s not super uncommon for people to die of sudden cardiac death and later be found to have had the disease,” Dr. Pryma explained. “We don’t know exactly how many of those people there are."

One famous example of a patient who was misdiagnosed is the 34th President of the United States, Dwight Eisenhower. Eisenhower struggled with intense headaches and high blood pressure for much of his career. It wasn’t until after his death that an autopsy revealed a pheochromocytoma, a hormone-secreting tumor in the adrenal glands.

Because they typically grow and spread, neuroendocrine tumors can be difficult to treat. According to Dr. Pryma, there are some blood pressure medications that can block the fight-or-flight effects of the disease, but these drugs often come with equally debilitating side effects such as fatigue and depression.

Neuroendocrine tumors can sometimes grow into the blood vessels or are located near sensitive areas of the body (near the aorta or the kidney), removing the option for safe surgical resection. Ideally, Dr. Pryma says, the goal is to treat the tumors without causing any additional side effects.

The Right Treatment, the Best Care

Azedra is the only FDA-approved treatment for people who are ineligible for surgical resection of their neuroendocrine tumors. As Dr. Pryma explains, the radiotherapy drug is administered via IV. Unlike traditional radiation, Azedra goes throughout the body, hones in on problem cells, and delivers radiation directly to those specific cells.

“We couldn’t safely give external radiation to a patient who has disease disseminated all over their body, in many different sites,” Dr. Pryma said, “You can do that with this drug.”

The Penn-led trial showed Azedra stopped tumor growth and reduced cardiovascular side effects in study participants. But Dr. Pryma insists effective care of rare neuroendocrine cancers is not only about providing new treatment options, it’s about building a multidisciplinary, expert care team.

Penn is one of the few academic medical centers in the country that has a tumor board that is dedicated to these rare cancers. Because neuroendocrine tumors release hormones, patients often need access to experts across a variety of specialties. Penn’s tumor board includes surgeons, pathologists, medical oncologists and radiation oncologists, as well as receiving paramedics, nephrologists and gastroenterologists.

“We know that tumor boards improve patient care. When you get all the different specialists together in one room to discuss patients, less falls through the cracks and you get a variety of opinions that are very helpful,” Dr. Pryma said.

“Not every patient with this disease will benefit from this particular treatment but having that expert team, getting the patient connected with that team and having them evaluated for various treatments can open the door to better care."

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The Focus on Cancer blog discusses a variety of cancer-related topics, including treatment advances, research efforts and clinical trials, nutrition, support groups, survivorship and patient stories.

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