Balance, gait negatively impacted after chemotherapy treatment

A single chemotherapy treatment can result in a significant negative impact on walking gait and balance, putting patients at an increasing risk for falls, according to a new study involving breast cancer patients conducted by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). Up to 60 percent of patients experience chemotherapy-induced peripheral neuropathy (CIPN), nerve damage that impacts feeling in the hands or feet; however, when and to what extent this damage impacts functional abilities has been largely unknown.

This new study is the first to objectively measure the functional abilities of cancer patients during and after taxane-based chemotherapy. Researchers followed 33 patients with stage I-III breast cancer, assessing functional performance (standing balance and gait) and patient-reported outcomes at five timepoints spanning before treatment began up to three months post-treatment completion.

Researchers observed a 28 percent increase in side-to-side sway (medial-lateral) after just one chemotherapy treatment. That increased to 48 percent with cumulative chemotherapy exposure. Patients also demonstrated a 5 percent reduction in walking speed after three cycles of chemotherapy.

This is not simply a quality of life concern – CIPN can impact a patient’s ability to receive treatment at all, limiting the potential for a cure. For patients who have great difficulty with neuropathy, we often have to modify their treatment regimen to make it tolerable – sometimes the therapy has to be ceased entirely,” says Maryam Lustberg, MD, MPH, senior author of the study and director of breast cancer survivorship services at the OSUCCC – James. “We need to make these treatments more tolerable to patients so they can get the full benefit of the treatments.”

Lustberg and her colleagues report that taxane exposure is also associated with worsened sensory symptoms and poorer postural control. There was also an association between patients’ balance and self-reported sensory symptoms.

Significant Clinical Problem

CIPN leads to pain, falls and difficulty walking as well as performing activities of daily living. Although symptoms can improve with time, up to 30 percent of patients have persistent symptoms that last at least six months.

Researchers say the study provides initial support for the feasibility and potential utility of implementing objective measures of physical function into the oncology clinic.

Cancer survivors are at a significant increased risk for falls, and the incidence rate of falling after chemotherapy is a serious concern for survivors’ long-term quality of life,” adds Lustberg. “Our study provides new insights on how taxane-based chemotherapy can impact fundamental aspects of patient function. These new insights can help us develop better strategies to help patients combat these challenges and, in some cases, choose a different therapy to treat the disease but with reduced side effects.”

The OSUCCC – James is expanding this research to assess CIPN in colorectal cancer patients receiving taxane-based chemotherapy.

Integrating Gait, Balance Testing Into Clinical Practice

Study co-author Ajit Chaudhari, PhD, associate professor of physical therapy, orthopedics, mechanical engineering and biomedical engineering at The Ohio State University Wexner Medical Center says the study was an important first step in achieving better long-term outcomes after cancer and provides a new tool for integrating gait and balance screening into clinical care.

We have created an easy-to-use clinical tool that has strong potential to quickly help clinicians identify patients – very early on – who are developing a chemotherapy reaction that impacts gait and balance,” says Chaudhari. “It’s no longer good enough for someone to just ‘survive’ cancer because many patients have decades of life ahead of them. It is critical to do everything we can to make the rest of their lives as productive and enjoyable as they want it to be.

Monfort et al. Gait, balance, and patient-reported outcomes during taxane-based chemotherapy in early-stage breast cancer patients. Breast Cancer Res Treat. 2017; doi: 10.1007/s10549-017-4230-8 [Abstract]

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Chemotherapy and exercise: The right dose of workout helps side effects

Researchers at the University of Rochester Wilmot Cancer Institute discovered something simple and inexpensive to reduce neuropathy in hands and feet due to chemotherapy – exercise.

The study, involving more than 300 cancer patients, is to be presented this weekend and honored as a “Best of ASCO” among 5,800 abstracts at the world’s largest gathering of oncologists, the American Society of Clinical Oncology (ASCO) annual meeting 2016. More than a dozen other Wilmot scientists also were invited to present data at the meeting.

Investigators in the exercise study directly compared the neuropathic symptoms in non-exercisers to the pain among patients who took part in a specialized six-week walking routine with gentle, resistance-band training at home.

The exercisers reported significantly fewer symptoms of neuropathy – which includes shooting or burning pain, tingling, numbness, and sensitivity to cold – and the effects of exercise seemed to be most beneficial for older patients, said lead author Ian Kleckner, Ph.D., a biophysicist and research assistant professor in Wilmot’s Cancer Control and Survivorship program. Kleckner also won an ASCO Merit Award in the pain and symptom management category, and was invited to give a talk about his work.

Not all chemotherapy drugs cause neuropathy, but 60 percent of people with breast cancer and other solid tumors who receive taxanes, vinca alkaloids, and platinum-based chemotherapies will likely suffer this type of side effect, Kleckner said. Neuropathy is more commonly associated with diabetes or nerve damage. No FDA-approved drugs are available to prevent or treat chemotherapy-induced neuropathy, he added.

Wilmot’s specialized exercise program, called EXCAP (Exercise for Cancer Patients), was developed several years ago at the UR by Karen Mustian, Ph.D., M.P.H., an associate professor in the Cancer Control program. In recent years she has copyrighted and evaluated EXCAP in several clinical trials. Last year at ASCO, Mustian presented data from a randomized, controlled study of 619 patients showing that EXCAP reduced chronic inflammation and cognitive impairment among people receiving chemotherapy. Kleckner’s study involved a subset of patients from Mustian’s trial, which is the largest phase 3 confirmatory exercise study ever conducted among cancer patients during chemotherapy. Their work is funded by the National Cancer Institute and Mustian’s PEAK lab.

Exercise – as a cancer prevention tool and potential treatment – is a hot topic among the nation’s oncologists and their patients.

Kleckner, a longtime drug-free body builder and former college rugby player, said he’s committed to understanding more deeply the benefits of exercise for cancer patients. “Exercise is like a sledgehammer because it affects so many biological and psychosocial pathways at the same time – brain circuitry, inflammation, our social interactions – whereas drugs usually have a specific target,” he said. “Our next study is being designed to find out how exercise works, how the body reacts to exercise during cancer treatment, and how exercise affects the brain.”

Mustian is also giving two talks at ASCO, about the use of exercise in geriatric cancer patients and how innovation can help exercise investigators reach their goals.

Our program at the University of Rochester, which now includes more than  half a dozen researchers, is becoming a real powerhouse in exercise oncology,” Mustian said. “Twelve years ago when we started this work a lot of people said it was not safe for most cancer patients to exercise. Now we know it can be safe when done correctly, and that it has measurable benefits. But more exercise isn’t always better for patients who are going through chemo – so it’s important to continue our work and find a way to personalize exercise in a way that will help each individual.”

Evaluation of mangafodipir treatment for oxaliplatin-associated neuropathy

An unfortunate side effect of the platinum-chemotherapy drug oxaliplatin is the development of neurotoxicity, which can adversely affect a patient’s quality of life; therefore, the benefit of oxaliplatin-based therapy must be balanced with prevention of neuropathies. Currently, there are no therapeutic interventions available to relieve oxaliplatin-associated neurological symptoms, which are thought to be a result of reactive oxygen species-associated damage.

In this issue of the Journal of Clinical Investigation, Frédéric Batteux and colleagues at the Laboratoire d’Immunologie evaluated use of the MRI contrast agent mangafodipir, which has antioxidant properties, for relief of oxaliplatin-associated neuropathies. In a mouse model of oxaliplatin-induced neurologic damage, administration of mangafodipir reduced neurotoxicity and the presence of oxidized protein products. Furthermore, in a cohort of 22 patients with oxaliplatin-associated neuropathy, mangafodipir treatment appeared to decrease neurological symptoms.

In their accompanying commentary, Charles Loprinzi and colleagues at the May Clinic caution that even though these results seem promising, larger clinical trails have not been able to confirm similar results from other agents that have shown promise for treating chemotherapy-induced neuropathy in animal models and small phase II trials.

Coriat et al., (2014). Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir. J. Clin.Invest., 124:262–272. doi:10.1172/JCI68730 [Article]

Pachman et al., (2014). The search for treatments to reduce chemotherapy-induced peripheral neuropathy. J. Clin. Invest., 124:72-74. doi:10.1172/JCI73908 [Abstract]