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‘Symptom science’ aims to ease burden of cancer treatment

Team of OHSU researchers working to discover better ways to control cancer symptoms, toxic side effects of treatments to improve quality of life for people battling cancer
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Clifford Alexander, left, sits on a medical room bed and gets a check-up by OHSU physician assistant Jeff Donovan, P.A.-C., who is standing to Clifford's right, at the OHSU Center for Health and Healing building. (OHSU/Christine Torres Hicks)
Clifford Alexander, left, gets a check-up with OHSU physician assistant Jeff Donovan, P.A.-C. (OHSU/Christine Torres Hicks)

The diagnosis — stage 4 colon cancer — arrived like a bolt from the blue. And at first, Clifford Alexander could think only about the fight to survive. But as the shock wore off, and with treatment successfully underway, Alexander started to think more about living with cancer. Would he be forced to stop doing the things he loved?

“You hear what chemo can do, leave you nauseated and exhausted,” he said. In his case, one of the most troubling chemo side effects was damage to peripheral nerves — those outside of the brain and spinal cord — called peripheral neuropathy. “It built up to where I couldn’t tie fishing flies anymore; I couldn’t feel the fine threads. I really didn’t want to have to give that up.”

Alexander didn’t hesitate to volunteer when his doctor told him about a study testing a drug meant to stop chemo-induced neuropathy. That clinical trial is part of an expanding new program of “symptom science” research at Oregon Health & Science University. The team includes researchers in the basic biology of cancer; oncology, nursing and palliative care; and nutrition and rehabilitation.

Eric Roeland and team
Eric Roeland, M.D. (OHSU)

“Our focus is on trying to determine the cause of distressing symptoms, and finding the best way to prevent and treat those symptoms,” said medical oncologist Eric Roeland, M.D., an associate professor of medicine (hematology and medical oncology) in the OHSU School of Medicine. He joined the OHSU Knight Cancer Institute two years ago with the mission to develop a research program focused on minimizing treatment-related toxicity and improving the quality of life of people living with cancer.

“It’s easy for an oncologist to stand at a podium and say that an exciting new drug was ‘well-tolerated,’ but I can tell you that people experiencing even low-grade symptoms over time would not agree,” Roeland said. “Don’t get me wrong; cancer-directed therapies are revolutionizing the care of patients living with cancer. But as urgently as we develop new therapies, we just as urgently need to determine best strategies to make them as tolerable as possible so that people can live their lives.”

Improving quality of life during cancer

Because cancer research historically focused intently on seeking cures, many treatments for symptom management remain largely based on limited evidence from small pilot studies or case reports rather than more definitive controlled clinical trials.

Sarah Lowry, D.N.P. (OHSU)
Sarah Lowry, D.N.P. (OHSU)

“There’s a potential that we're missing things with that lack of evidence,” said Sarah Lowry, D.N.P., an assistant professor of medicine (hematology and medical oncology) in the OHSU School of Medicine and member of the symptom science research group. “Symptom science is being more thoughtful and intentional about creating studies that will point the way to improved quality of life.”

Consider the cancer treatments called immune checkpoint inhibitors: These agents dramatically improved outcomes for people with some types of cancer. Initial studies suggested that they would be easier on patients than chemotherapy and safer to give to fragile individuals. Years of experience have revealed a fuller picture of side effects, and recent reports suggest that women are at risk of developing more adverse reactions than men.

Deanne Tibbitts
Deanne Tibbitts, Ph.D. (OHSU)

At OHSU, Deanne Tibbitts, Ph.D., a research assistant professor (oncological sciences) in the OHSU School of Medicine, is leading a clinical trial designed to reveal how the side effects of checkpoint immunotherapy change over time, and whether side effects are different depending on the sex or gender of the patient. The eventual goal is to find ways to identify those most at risk of toxic effects and be ready to intervene more aggressively to prevent severe symptoms.

In this approach, patient-reported outcomes are the focus, not what clinicians document in their notes about side effects. Researchers are gathering first-hand accounts from patients about how they're feeling, how severe their symptoms are, and how much that is impacting their quality of life — which is not typically done in cancer clinical trials. “By going directly to patients and asking them to share how they are feeling, we hope to learn about the missing pieces we need to help providers take better care of people on checkpoint inhibitors,” Tibbitts said.

Severe weight loss and muscle wasting from cancer, a syndrome called cachexia, are among the harshest and difficult-to-treat symptoms. Roeland recently opened a clinical trial of a potential drug treatment. The drug, olanzapine, targets neurotransmitters — the brain’s messenger molecules — that are involved in controlling appetite and energy balance. Olanzapine’s original purpose was treating psychotic illness, but it has been repurposed and shown some benefit in preventing chemo-induced nausea and possibly impacts on appetite.

Roeland’s study is testing the generic drug’s effectiveness against cachexia in a controlled clinical trial in which some participants will get olanzapine and others, selected randomly, will get an inactive placebo. The study will measure the effects on appetite and food intake, weight loss, muscle wasting, physical function, patient-reported symptoms, quality of life, toxicity and health care use.

It is an investigator-initiated study not sponsored by any drug company. “There’s no big money backing work in this space,” said Roeland, who secured funding from the OHSU Knight Cancer Institute and the National Cancer Institute of the National Institutes of Health.

Clinical trials upcoming, underway

Among other planned studies, the group hopes to begin testing a drug to relieve hot flashes and other symptoms caused by androgen deprivation therapy for prostate cancer; the therapy reduces a patient’s testosterone levels. “There have been several studies looking at interventions for women going through treatment for breast cancer, but there's substantially less interest and data for men going through hormone therapy for prostate cancer,” Lowry said.

Kerri Winters-Stone, Ph.D. (OHSU)
Kerri Winters-Stone, Ph.D. (OHSU)

Chemo-induced peripheral neuropathy, the damage to nerves outside of the brain and spinal cord, is a major focus area. In many cancer survivors, symptoms persist after treatment ends, limiting movement and increasing the risk of falls. In a study in collaboration with Kerri Winters-Stone, Ph.D., a professor of medicine (oncological sciences) in the OHSU School of Medicine, researchers are seeking ways to predict which patients are most likely to develop neuropathy symptoms that impair mobility and increase fall risk by tracking the trajectories of symptoms, functioning and falls before, during and after treatment in adults prescribed neurotoxic chemotherapy for cancer. The goal is to help identify individuals who would benefit from early and targeted preventive measures.

Alexander, who was diagnosed with stage 4 colon cancer in the fall of 2022, can’t say whether the experimental drug in his study has limited his peripheral neuropathy. Because the trial is a randomized, placebo-controlled study, he doesn’t know if he took the study drug or the placebo. Alexander gladly volunteered, viewing it as a way of contributing after receiving care from so many nurses and doctors.

He has worked hard to adapt to limitations and rebuild strength by exercising and eating healthy foods. Last spring, he resumed fishing and hunting, including a three-day turkey hunting trek in the wilderness. He credits much to the support from his wife, Nicole Alexander.

“Every day we are grateful that he can tolerate chemotherapy so amazingly well,” she said. “His side effects have been so well-managed.”

“I don’t know how this is going to work out for me in the end,” her husband said. “I’m learning to find the good in each day. That’s enough for me right now.”

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