Chemotherapy-induced peripheral neurotoxicity: A critical analysis

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Introduction

As a consequence of advances in cancer diagnosis and treatment, there are now an estimated 28 million cancer survivors worldwide.[1] As such, long-term quality of life is an increasingly important issue, with 67% of U.S. cancer patients surviving at 5 years. Addressing the long-term toxicities of cancer treatment is critical due to their potential impact on cancer survivorship.[2] Accordingly, there has been a gradual shift in focus toward postchemotherapy recovery and survivorship, with an awareness of the importance of the individual patient experience, patient-reported outcomes, and the long-term effects of treatment. Of particular importance is chemotherapy-induced peripheral neuropathy (CIPN), which can lead to permanent symptoms and disability in up to 40% of cancer survivors.[3] CIPN can be a significant disability following the treatment of many types of cancer, including breast, colorectal, testicular, and hematological malignancies, and have an impact on quality of life. As such, there is a critical need to understand pathophysiological mechanisms, optimize clinical assessment, and develop neuroprotective strategies to prevent neuropathy. This review will address the challenge of CIPN, highlighting treatment-related neuropathy caused by some of the most commonly used chemotherapeutic agents (such as taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib), and provide recommendations regarding assessment strategies, management, and follow-up.....


"The benefits of including direct patient evaluations include a more comprehensive and accurate assessment of CIPN, improved understanding of the impact of CIPN symptoms on the patient, and a better correlation of toxicity findings with functional outcomes."

 

Table 1. Chemotherapies Associated With Peripheral Neuropathy

Table 2. Assessment of CIPN Via Neuropathy Grading Scales

  

Table 3. Chemotherapy Dose and Duration as a Risk Factor for CIPN

Table 4. Current Clinical Trials in the Prevention and Treatment of CIPN

Table 5. CIPN Recommendations and Strategies 

Conclusions

CIPN remains a clinically significant and potentially serious side effect of cancer treatment, with increasing relevance to the millions of cancer survivors worldwide. The number of cancer survivors with disability due to CIPN is underreported, as the use of patient-reported outcomes and objective assessment tools typically reveal greater neurotoxicity than clinician assessment. Improved understanding concerning the pathophysiology underlying the development of CIPN and the diverse mechanisms across different chemotherapies seems crucial to the development of future neuroprotective strategies. Appropriate, standardized, and objective assessment tools combined with validated instruments that also document patient-reported symptoms will be necessary to identify the long-term impact of CIPN in cancer survivors. The dividend of improved cancer outcomes with advances in treatment may be compromised if we fail to develop approaches to minimize the chronic consequences of toxicities such as CIPN (Table 5).