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Risk Factors for Chemotherapy-Induced Peripheral Neuropathy

Nalley, Catlin

doi: 10.1097/01.COT.0000732260.73501.dd
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Chemotherapy
Chemotherapy:
Chemotherapy

A recent study demonstrated that patients with low pre-treatment hemoglobin, higher BMI, and older age are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting and serious side effect of neurotoxic cancer treatments, including taxanes and platinum agents.

These research findings were recently presented at the ESMO Asia Virtual Congress 2020 (Abstract 334MO). Future prospective research is needed to determine if correcting hemoglobin and BMI mitigates CIPN development, according to the study authors.

“With survival rates of cancer increasing globally, there's an increased focus on survivorship and symptom management,” noted study author David Mizrahi, PhD, with the Prince of Wales Clinical School at UNSW in Sydney, Australia. “One dose-limiting and debilitating side effect of chemotherapy is CIPN, which affects around half of cancer survivors both during and persisting after treatment.

“Changes in sensation such as numbness and tingling are very common. Also, pain can occur, as well as impaired balance,” he continued. “Yet, identifying patients who are at increased risk of developing CIPN remains a challenge and there's limited data on routinely measured pretreatment factors such as blood-based or clinical factors that are predictive of CIPN.”

Study Details

In an effort to address this knowledge gap, Mizrahi and colleagues sought to identify the association between pretreatment blood-based and clinical factors with the development of CIPN following treatment. The study included patients who received paclitaxel or oxaliplatin 3-12 months prior. They also had a routine blood sample within 1 month of starting chemotherapy.

“Our primary method of assessing CIPN was using the total neuropathy score, which is a composite clinical grading measure of sensory assessments, deep tendon reflexes, manual muscle testing, and patient-reported symptoms,” Mizrahi said. “We had secondary assessments as well, including the grooved pegboard to assess upper body function, and the clinically graded CTCAE.”

To compare post-treatment CIPN severity, researchers used blood-based biomarkers within 30 days prior to beginning chemotherapy. “Independent samples t-tests with post-hoc Bonferroni correction were used to compare CIPN between patients according to blood-based biomarker normative ranges, with significance adjusted to p<0.006,” the study authors outlined. “Linear regression was used to identify blood-based and clinical biomarker associations with CIPN development.”

This cross-sectional study recruited 333 patients. The majority received paclitaxel (n=228), 80 percent were female, and the mean age was 57.6±12.3 years. The most common disease types were breast, colorectal, and gynecological cancers. The majority of patients had persisting CIPN after treatment, with grade 1 CIPN or greater occurring in 73 percent of individuals.

The researchers found that routinely available pretreatment clinical and blood-based factors were useful in predicting post-treatment CIPN. “In our multivariate regression model, we identified that patients with a higher TNS score, which indicated worse CIPN, who were of older age were more likely to develop neuropathy,” explained Mizrahi.

“We also found that patients who had a higher body mass index were more likely to develop CIPN,” he reported. “And, interestingly, we found that patients with low hemoglobin at pretreatment levels were also more likely to develop CIPN.”

When the investigators looked at the chemotherapy separately, they observed that patients who were older and had low hemoglobin before treatment were also more likely to have CIPN following chemotherapy, according to Mizrahi.

This finding led the researchers to separate patients by those who had low hemoglobin using the reference ranges at their hospital. Low hemoglobin was defined as less than 130 g/L in males and less than 120 g/L in females. Twenty-five percent of patients had low hemoglobin before neurotoxic chemotherapy.

“We compared those patients to those who had normal hemoglobin levels and we found that these patients experienced worse CIPN after treatment with impaired hemoglobin before treatment,” stated Mizrahi, who noted that this was shown in the TNS scores, as well as “the pegboard time showing decreased upper body functional capacity perhaps due to sensory changes.

“So, in conclusion, we identified that older patients, those with a higher BMI and low hemoglobin before treatment, are at increased risk of developing paclitaxel- or oxaliplatin-induced peripheral neuropathy,” he summarized. “Patients with these routinely accessible factors may warrant closer monitoring of CIPN, both before starting treatment and ongoing throughout treatment.”

Mizrahi noted that prospective research is warranted to further explore the impact of both hemoglobin and body mass index, which change over time, on the development of CIPN. “Future studies may also wish to investigate the effect of correcting pretreatment anemia on long-term CIPN outcomes,” he concluded.

Catlin Nalley is a contributing writer.

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