Neuromuscular Training Decreased Incidence of Chemo-Induced Peripheral Neuropathy

Neuromuscular training decreased the onset of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients, a randomized trial showed.

Among patients who were receiving either oxaliplatin or vinca alkaloids in the intention-to-treat analysis, the incidence of CIPN was 30% for those participating in sensorimotor training (SMT) and 41.2% for those participating in whole-body vibration (WBV) training compared with 70.6% for those receiving usual care (P=0.002), reported Fiona Streckmann, PhD, of the University of Basel in Switzerland, and colleagues.

Furthermore, results were more pronounced in a per-protocol analysis (>75% participation in the intervention):

• SMT group: 28.6%
• WBV group: 37.5%
• Usual care group: 73.3%

“Based on our results as well as the current literature, this specific exercise regimen not only presents potentially the best current treatment option for CIPN but also has the potential to prevent CIPN, improve quality of life, and have a positive impact on the course of oncological treatment,” Streckmann and team wrote in JAMA Internal Medicine.

They noted that CIPN is a “highly prevalent and clinically relevant” adverse effect of chemotherapy, and oxaliplatin and vinca alkaloids induce acute CIPN, with incidences of 70% to 90%, and chronic CIPN, with incidences of 50%. Symptoms, including loss of sensation, tingling, dysesthesia, pain, and loss of balance, affect activities of daily living and reduce quality of life.

“Positive results have been achieved with specific exercise interventions due to their wide range of proregenerative effects, including expression of growth factors, altered blood perfusion, and enhanced mechanoreceptor sensitivity,” they added. “Neuromuscular stimulating interventions, such as SMT or WBV training, seem especially beneficial because they address both sensory and motor symptoms.”

SMT is focused on balance and increasing mobility, while WBV training is believed to improve gait stability and muscle strength.

In an accompanying commentary, Arjun Gupta, MD, of the University of Minnesota in Minneapolis, and colleagues wrote that the study “supports the use of supervised exercise and physical medicine programs in reducing the risk of incident CIPN while receiving chemotherapy. As the evidence supporting these interventions grows, we must ensure that we have the capacity and incentives in place so patients can harness these benefits and live their fullest lives.”

The study included 158 patients (mean age 49 years, 59% men) from four German centers, most of whom had lymphoma or colorectal cancer. They were randomized into three groups: supervised SMT or WBV training sessions twice a week for about 15 to 30 minutes or usual care.

SMT consisted of balance exercises on progressively unstable surfaces that increased with difficulty. Each patient performed four exercises per session, with each performed three times for 20 seconds, allowing a 40-second rest between each set and a 1-minute rest between each exercise. WBV training took place on a side-alternating vibration platform with patients standing on their forefeet, performing four sets of 30- to 60-second vibration periods.

Training sessions started 24 to 72 hours after randomization and were continued until completion of medical therapy. The primary aim of the study was to reduce the incidence of CIPN, as detected via a thorough neurological assessment.

The mean compliance rates were 68% for usual care, 78.2% for SMT, and 71.7% for WBV training. Patients in the intervention groups performed an average of 18 of 20 training sessions.

Streckmann and colleagues also reported differences in secondary outcomes between the groups.

For example, in the SMT group, there were fewer dose reductions of medical therapy compared with the usual care and WBV groups (31.6% vs 56.4% and 53.8%, respectively). Moreover, they noted that there was lower mortality in the 5 years after completion of chemotherapy in the SMT group that reached statistical significance compared with the usual care group — 1.9% versus 17.1% (P=0.04).

Patients in the SMT group also reported significantly less pain and burning sensation than in the WBV or usual care groups.

Both the SMT and WBV groups improved balance control in bipedal stance. Patients in the SMT group also had improved bipedal stance with eyes closed and monopedal stance.

The editorialists noted that while the results of the study were encouraging, it came with some limitations.

They observed, for example, that the median age of the study cohort was 49 years — a full two decades younger than the median age of people with cancer diagnoses in the U.S.

They also pointed out that one-fourth of trial participants in the intervention arms did not meet the criteria for the per-protocol analysis.

“This highlights how delivering the intervention can be challenging, but demonstrating benefits in the intention-to-treat analysis despite suboptimal adherence speaks to the possible efficacy of the interventions,” they wrote.

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