Elsevier

European Journal of Cancer

Volume 46, Issue 3, February 2010, Pages 479-494
European Journal of Cancer

Review
Chemotherapy-Induced Peripheral Neurotoxicity assessment: A critical revision of the currently available tools

https://doi.org/10.1016/j.ejca.2009.12.008Get rights and content

Abstract

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a frequent, potentially severe and dose-limiting side-effect of cancer treatment. Despite its clinical relevance that limits the use of several antineoplastic agents and even the future development of new anticancer drugs, several crucial aspects of CIPN remain unsolved, one of which is how to assess its occurrence and severity in the most effective and reliable way.

CIPN severity is generally assessed using Common Toxicity Criteria (CTC) scales, although it is well known that significant inter-observer disagreement exists using these scales. Moreover, most CTC scores mix impairment, disability and quality of life measures, which could lead to misinterpretation of the results and unpredictable under- or overestimation of the effect. This uncertainty may lead to different interpretations of the results of the same clinical trials by clinicians and also by regulatory agencies. The use of other types of scale based on clinical and instrumental examinations, or the use of self-administered questionnaires for patients, has not yet really improved the accuracy of CIPN assessment, although some of these tools are promising and deserve to be further validated. As a result, there is a general recognition that CIPN has still not been properly assessed and that improvements should be made.

In this review, the available data regarding the different tools used to assess CIPN will be revised and their features will be critically examined, with a special focus on their reliability and reproducibility across examiners and, when available, through direct comparison.

Introduction

In routine practice, Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is evaluated using clinical and paraclinical parameters. The role of instrumental examinations in CIPN patients is questionable in clinical practice and it is our opinion that they are really useful only in unusual cases or, sometimes, in the follow-up of selected patients with a particularly severe CIPN. The reasons for this limited usefulness of the electroneurography (ENG) of peripheral nerves are several, mostly related to the localisation of the primary site of toxic action of the drugs that prevents reliable investigation (e.g. the primary dorsal root ganglia damage with platinum compounds, with delayed involvement of the peripheral nerves explored by ENG) or to the type of nerve fibres’ involvement (e.g. small myelinated and unmyelinated fibres damage during bortezomib treatment, while ENG can only detect large myelinated fibres’ impairment). Electromyography (EMG) is painful, disturbing for the patients and it gives only a non-quantitative assessment of motor units’ activity damage in the rare cases where motor impairment is severe and, therefore, already easily evaluable clinically. Semi-quantitative assessment of sensory threshold or of muscle strength has also occasionally been proposed, but standardisation of the instruments and of the methods to be used has never been achieved. Therefore, CIPN assessment should be based on effective and reliable clinical methods. Usually, objective assessment of neuropathic signs is performed with bedside clinical examinations (e.g. search for sensory and motor abnormalities, deep tendon reflex changes, orthostatic hypotension and constipation). Recently, increased attention has been focused on the patients’ perception of CIPN severity and effects, and several patient-reported questionnaires have been developed to overcome the obvious limitation of the patient interview that is part of the routine medical examination.

The following sections will summarise, in a non-systematic revision, the background and the main characteristics of the scales most widely used until now to grade CIPN, with particular reference to their ability to detect and report the proposed aspects of CIPN and the exclusion of pain-specific scales because they have already been extensively reviewed in the recent literature, and none of them has been designed or validated to assess the occurrence of neuropathic pain in CIPN.1

Section snippets

Common Toxicity Criteria (CTC) scales

The following are the available CTC scales developed by established organisations and commonly used in clinical practice to report CIPN (Table 1).

Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group (GOG)-neurotoxicity (FACT/GOG-Ntx)

In 1998 the GOG, collaborating with the Author of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, developed the FACT/GOG-Ntx subscale.9 The FACT/GOG-Ntx is a 38-item self-reported questionnaire consisting of two components: a 27-item general measure of quality of life (FACT-G) and a 11-item neurotoxicity subscale (Ntx subscale) targeting symptoms and patients’ concerns thought to be specifically associated with CIPN and also covering activity impairment (Table 2

Quality of life (QoL) assessment

The assessment of QoL in cancer patients is a relatively recent issue despite its clear clinical relevance given the increasing number of long-lasting cancer survivors achieved by improvement in cancer treatment. The use of general QoL scales in clinical trials and daily practice has the main aim of providing a more accurate evaluation of the well-being of the patients as well as of the benefits and side-effects that may result from medical intervention. However, only one of the available QoL

Composite scales

Composite scales have recently been proposed to improve the accuracy, reliability and effectiveness of the assessment of CIPN and they have generally been developed by neurologists. However, despite the several theoretical advantages they may offer in the accurate neurological assessment of CIPN (e.g. discriminating among the different types of sensory impairment, giving a precise topographical localisation of the signs and symptoms, making it possible to perform the evaluation through a

Conclusion

From the available literature it appears that the existing scales currently being used are not satisfactory for evaluating CIPN. Moreover, evidence is emerging that health-care professionals tend to underestimate and underreport the severity and frequency of CIPN, especially the subjective symptoms such as fatigue and numbness, which impact on the patient’s QoL. Therefore, better instruments to measure the severity of toxic neuropathy are needed for clinical management and for trials of

Conflict of interest statement

None declared.

References (32)

  • T.J. Postma et al.

    Grading of chemotherapy-induced peripheral neuropathy

    Ann Oncol

    (2000)
  • H.Q. Huang et al.

    Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a Gynecologic Oncology Group Study

    Int J Gynecol Cancer

    (2007)
  • E.A. Calhoun et al.

    Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy

    Int J Gynecol Cancer

    (2003)
  • D. Cella et al.

    Measuring the side effect of taxane therapy in oncology

    Cancer

    (2003)
  • L. Almadrones et al.

    Psychometric evaluation of two scales assessing functional status and peripheral neuropathy associated with chemotherapy for ovarian cancer: a gynecologic oncology group study

    Oncol Nurs Forum

    (2004)
  • G.D. Leonard et al.

    Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer

    BMC Cancer

    (2005)
  • Cited by (0)

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