Working Toward Better Radiation Responses Through Novel, Targeted Drugs
, by Kendall Morgan, NCI-CONNECT Contributor
Radiation oncologist Dr. Kevin Camphausen is helping people with brain and spine tumors by developing drugs that can enhance the radiation impact with the goal to improve patient outcomes.
For people diagnosed with glioblastoma (GBM) or other brain or spinal cord cancers, radiation treatment remains a cornerstone of almost all treatment programs. Unfortunately, while radiation comes with survival advantages, in most GBM cases today the primary cancer ultimately comes back.
Radiation oncologist Kevin Camphausen, M.D., and his lab at the National Cancer Institute’s Center for Cancer Research, is working to change this by developing and testing molecularly targeted drugs for use in combination with radiotherapy. Known as radiation sensitizers, these drugs aim to improve radiotherapy responses by making tumors more sensitive to radiation.
“The majority of treatments for patients fail at the primary tumor site,” Camphausen says. “That’s because surgery and local radiation, even together with chemotherapy, are not good enough. We’re developing drugs that should enhance the radiation killing effect with the goal to improve outcomes for patients.”
Caring for Patients
Patients with a wide range of brain and spinal cord cancer types will receive radiation therapy at some point over the course of treatment. When patients’ with brain or spinal cord tumors need radiation treatments at NCI, the NCI-CONNECT team and other members of the clinical team in the Neuro-Oncology Branch work with Dr. Camphausen and the Radiation Oncology Branch to provide these services. Dr. Camphausen reports that they offer the standard of care, most often to patients living nearby or in the surrounding area. They refer many others to clinics closer to home to make regular radiation treatments easier.
“Radiation is every day, Monday through Friday, for six weeks,” he says. “Transportation is a big deal. Most of our patients live within an hour. If they live farther away, we refer them out.”
But Dr. Camphausen isn’t satisfied with the standard of care when it comes to radiation treatment. As he explains, advances in radiotherapy in the past have primarily involved dividing radiation doses, an approach called fractionation, improved dose delivery, and improved localization of radiation to the places where it’s needed. Intensity modulated radiation therapy (IMRT), which attempts to more precisely direct radiation to the tumor while limiting its impact on healthy tissue, may allow further improvements in the future. But, Dr. Camphausen says that such technical improvements are likely to provide only incremental benefits.
Making Treatment Advances
To make more significant strides, his lab studies the interaction of novel drugs and radiotherapy in the treatment of glioblastoma, both through studies in animal models and clinical trials in patients. As Chief of the Radiation Oncology Branch, he guides the clinical and translational program, which explores the role of new agents as both radiation sensitizers and radiation protectors. By integrating novel imaging, molecular profiling, and state of the art treatment techniques, his efforts ensure that the NCI Branch is at the forefront of radiation oncology.
As part of this effort, Dr. Camphausen reports that about one in every four patients who come to him with a newly diagnosed GBM will qualify for one of a few ongoing clinical trials. These include:
- A phase 1 clinical trial of a drug called selinexor in combination with the chemotherapy temozolomide (TMZ) and radiation therapy in patients with newly diagnosed glioblastoma. The trial is based in part of prior studies showing that the drug makes glioma cells more sensitive to radiation. Selinexor is already approved to treat multiple myeloma. The study in GBM will learn the highest dose of selinexor that people with brain cancer can tolerate when taken in combination with TMZ and radiation therapy.
- Another phase 1 clinical trial is testing repeat radiation therapy for patients with GBM whose tumor has come back after treatment with surgery, chemotherapy, and radiation therapy. The goal is to find the safest dose of radiation for people with recurrent GBM.
- In another clinical study, Dr. Camphausen and colleagues are collecting blood and urine samples from patients undergoing radiation therapy for GBM to see how treatment affects blood cells and certain proteins. The goal is to learn whether two proteins, in the blood can help to predict whether or not a tumor will come back at one year.
- Dr. Camphausen also leads another study that is enrolling NCI patients who receive radiation therapy and aren’t receiving any experimental treatment regimen. The goal is to assess the late effects of treatment on individuals and their disease over time.
Words of Advice
For people who may have received a diagnosis of GBM or another brain or spinal cord tumor, Dr. Camphausen recommends finding a specialist to help with treatment decisions, whether you are considering a clinical trial or not.
“It’s really important to reach out to people that specialize in brain tumors, whether it’s at the Neuro-Oncology Branch or another large cancer center,” he said. “Most GBM tumors recur and it’s important to get right treatment up front.”
Dr. Camphausen says that sometimes patients may be treated in their communities in ways that will make them ineligible for clinical trials later.
Even if you are not on a trial, get the right imaging up front.
“You want to have the maximal safe surgery. If there’s a genomic test, do it up front and really understand your treatment options. People often are so overwhelmed with the diagnosis that they don’t do that. It’s understandable but it’s important to know that this can really limit your choices later.”
Wherever you may be, Dr. Camphausen recommends finding a place as close to you as you can where you will find doctors with lots of experience treating GBM or other rare brain and spinal cord tumors. One place you can reach out to for care and treatment options or referrals is the NCI’s Center for Cancer Research, Neuro-Oncology Branch and NCI-CONNECT, and Dr. Camphausen’s Radiation Oncology Branch.
“We are full service,” Dr. Camphausen says. “We have nurse practitioners, research nurses, clinical fellows, and a whole lab. All we do is study sensitizers. If you are asking yourself, ‘Where do I go for something novel or cutting edge?’, think of us.”