Chemotherapy-induced peripheral neuropathy (CIPN) is a common treatment-related adverse effect that can significantly affect long-term quality of life and interfere with cancer treatments. The pain can lead to reductions in chemotherapy doses and early discontinuation of the therapy. Studies estimate that about 38% of patients who are treated with multiple agents will develop CIPN, but this rate varies depending on the types of chemotherapy regimens used, duration of exposure to these agents, and how patients are assessed.
“CIPN is an important issue, especially within the context of the most commonly used chemotherapy regimens,” says Dawn L. Hershman, MD, MS. “Many of the drugs that have been evaluated for treating and preventing CIPN are agents that have documented efficacy for other common neuropathies. CIPN, however, is more difficult to manage than other neuropathies because there is greater variability in its pathophysiology and associated symptoms.”
A New Guideline
In 2014, the American Society of Clinical Oncology (ASCO) released a systematic review and evidence-based guideline on the management of CIPN in adult cancer survivors. The ASCO writing panel that developed the guideline systematically reviewed randomized controlled trials (RCTs) from the literature on managing CIPN, compared outcomes among trials, and provided guidance on the effectiveness of prevention and treatment options for CIPN in adults with a history of cancer. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life.
For the analysis, 48 RCTs met the eligibility criteria and comprised the evidentiary basis for the recommendations. “We studied many agents that have been used for CIPN, but few actually worked,” explains Dr. Hershman, who co-chaired the ASCO writing group that developed the guideline. “Overall, clinical trials tended to be small and many had insufficient sample sizes to detect any important differences in outcomes.” Primary outcomes varied across trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points.
Prevention & Treatment
On the basis of a paucity of high-quality evidence, the ASCO guidelines note that no agents are recommended for the prevention of CIPN (Table 1). “To treat existing CIPN, the best available data support a moderate recommendation for using duloxetine, but we still need more research on use of this drug for CIPN,” Dr. Hershman says (Table 2). Trials were inconclusive regarding tricyclic antidepressants, gabapentin, and a compounded topical gel containing a variety of active ingredients. ASCO reported that these agents may be offered—on the basis of data supporting their utility in other neuropathic pain conditions—given the limited options available to treat CIPN. The guideline panel noted that further research on these agents is warranted.
“Overall, the literature has shown that we lack effective therapies to treat cancer survivors suffering from CIPN,” says Dr. Hershman. “Some are promising or somewhat effective, but the benefits achieved with the currently available agents are small. These findings should serve as a call to action to conduct more research to explore the biologic drivers of CIPN so that we can better understand its pathogenesis. As we increase our understanding, we can use those lessons to help us develop new treatments.” Dr. Hershman adds that more data on the agents currently being used to treat CIPN are needed. Many of the studies reviewed did not consistently report adverse effects, an important missing component for helping make informed decisions about managing CIPN.
According to Dr. Hershman, there is an opportunity to decrease the incidence of CIPN if it is reported and recognized early. “We need to define the predictors of CIPN so that we can identify patients who may be at risk,” she says. “Clinicians are lacking a comprehensive and standardized approach to assessing CIPN, but this is vital to ensuring that we get reliable and valid data that can, in turn, enable us to better recognize, understand, and respond to CIPN.”
ASCO recommends that physicians should initiate discussions on the potential for CIPN when managing adult cancer survivors. It notes that patients may feel overwhelmed by their cancer diagnosis and treatment regimen; may not want to burden their healthcare providers with additional concerns; and may think that early CIPN symptoms are imaginary. “Clinicians need to address the intensity and symptoms of CIPN and treat patients empirically with what is available,” Dr. Hershman says. “There are some cases in which CIPN must be tolerated because of our limited treatment choices. However, there are other instances in which early recognition and intervention can guide changes in treatment regimens so that this adverse effect can be avoided.”
Readings & Resources (click to view)
Hershman DL, Lacchetti C, Dworkin RH, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Onc. 2014 Apr 14 [Epub ahead of print]. Available at: http://jco.ascopubs.org/content/early/2014/04/09/JCO.2013.54.0914.full.pdf+html.
Cavaletti G, Frigeni B, Lanzani F, et al. Chemotherapy-induced peripheral neurotoxicity assessment: a critical revision of the currently available tools. Eur J Cancer. 2010;46:479-494.
Pachman DR, Barton DL, Watson JC, et al. Chemotherapy-induced peripheral neuropathy: prevention and treatment. Clin Pharmacol Ther. 2011;90:377-387.
Argyriou AA, Bruna J, Marmiroli P, et al. Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol. 2012;82:51-77.