Worldwide, cancer chemotherapy is linked to chronic painful neuropathy for around 4 in every 10 patients treated with these drugs, suggests a pooled data analysis of the available evidence published by D’Souza et al in Regional Anesthesia & Pain Medicine.

Notwithstanding wide regional variations, platinum-based drugs, taxanes, and lung cancer seem to be associated with the highest rates of persistent painful neuropathy, defined as lasting at least 3 months, prompting researchers to call for tailored approaches to pain relief.

Study Background

Anticancer agents damage healthy cells and tissues, including the nervous system. The effects can manifest in movement disturbances, such as loss of balance or coordination, and sensory disturbances, such as loss of sensation; numbness, tingling, “pins and needles”; or a burning sensation on the skin.

Several factors influence the frequency and severity of chronic peripheral neuropathic pain, including type and dose of chemotherapy, preexisting neuropathy, and the use of other drugs that can damage the nervous system, explained the researchers.

The condition is thought to be caused by direct peripheral nerve cell damage which disrupts or rewires normal nerve signaling pathways, resulting in persistent pain, they added.

Prompted by the growing number of cancer survivors and increasingly aggressive treatment of the disease, the researchers wanted to gauge the global prevalence of chronic painful peripheral neuropathy linked to chemotherapy.

Study Design and Results

The team searched research databases for relevant studies published between 2000 and 2024, focusing on potentially influential sociodemographic, clinical, and methodological (such as study design and funding source) factors.

In all, they pooled the results of 77 eligible studies involving nearly 11,000 participants from 28 countries, all of whom had peripheral neuropathy that was associated with cancer drug treatment. In 4,545 of these participants, neuropathy was painful and persistent, lasting for at least 3 months.

The highest number of studies were carried out in the United States (n = 13) and Japan (n = 10), and almost half were prospective observational studies.

The cancers that featured most often in the studies were bowel (n = 25; 33%) and breast cancers (n = 17; 22%), while the largest proportion of studies focused on patients treated with either platinum-based agents (n = 13; 17%), or taxanes (n = 11; just over 14%), or both (n = 6; 8%), or the combination of leucovorin plus fluorouracil plus oxaliplatin (FOLFOX; n = 5; 6.5%).

Pooled data analysis of the study results showed that the overall prevalence of persistent painful peripheral neuropathy was just over 41%.

When stratified further, the analysis indicated that the highest prevalence was among patients treated with platinum-based agents (40.5%) and taxanes (just over 38%). Prevalence was lowest among those treated with the FOLFOX combination (16.5%).

Prevalence was also highest among those with primary lung cancer (just over 62%), possibly because of the complexities of treatment for this disease, suggested the researchers. Prevalence was lowest among those with primary ovarian cancer (31.5%) and lymphoma (36%).

When stratified by continent, studies of patients in Asia reported the highest prevalence of persistent painful neuropathy (46.5%), while studies of patients in Europe reported the lowest (36%). Prevalence rates were similar in both men and women.

The researchers emphasized that the design and methodology of the included studies differed substantially, and the overall certainty of evidence was considered to be low.

But they wrote: “Understanding the prevalence and predictors of chronic painful [chemotherapy-induced peripheral neuropathy] is critical for promoting early diagnosis and developing personalized treatment strategies. Our findings emphasize that chronic painful [chemotherapy-induced peripheral neuropathy] represents a substantial global health challenge, affecting more than 40% of those diagnosed with [it].”

The authors concluded, “The wide variability in prevalence rates across different countries, continents, chemotherapy regimens, and primary cancer history underscores the need for tailored strategies to address this debilitating condition. Future studies should focus on elucidating the mechanisms underlying these disparities and developing interventions that can reduce the burden of chronic painful [chemotherapy-induced peripheral neuropathy] globally.”

Disclosure: For full disclosures of the study authors, visit rapm.bmj.com.