Trial designs for chemotherapy-induced peripheral neuropathy prevention

Gewandter, Jennifer S.; Brell, Joanna M.; Cavaletti, Guido; Dougherty, Patrick M.; Evans, Scott; Howie, Lynn; McDermott, Michael P.; O’Mara, Ann; Smith, A. Gordon; Dastros-Pitei, Daniela; Gauthier, Lynn R.; Haroutounian, Simon; Jarpe, Matthew; Katz, Nathaniel; Loprinzi, Charles L.; Richardson, Paul G.; Lavoie-Smith, Ellen M.; Wen, Patrick Y.; Turk, Dennis C.; Dworkin, Robert H.; Freeman, Roy

doi:10.1212/wnl.0000000000006083

Cited by 72 publications

(59 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several recommendations have recently been published concerning the assessment of CIPN in the clinical trial setting . These have highlighted the unsuitability of the NCI‐CTCAE as a trial endpoint.…”

Section: Discussionmentioning

confidence: 99%

Overview and critical revision of clinical assessment tools in chemotherapy‐induced peripheral neurotoxicity

Park

Alberti

Kolb

et al. 2019

J Peripheral Nervous Sys

Self Cite

View full text Add to dashboard Cite

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major toxicity of cancer treatment, leading to dose reduction and premature treatment cessation, potentially affecting patient function, and quality of life. The development of accurate and sensitive assessment tools for CIPN is essential to enable clinical monitoring during treatment, follow-up of long-term outcomes and measurement of toxicity in clinical trials.This review examines CIPN clinical assessment scales incorporating clinician-based, composite, and patient-reported outcomes (PROs), providing a systematic review of their properties and an updated critical analysis of recommendations on current evidence for their use. This systematic review of CIPN assessment tools identified 50 papers containing 41 assessment tools, across 4 categories (common toxicity criteria; composite neurological scale; PROs; pain scale). The majority of these tools were PROs, underscoring the importance of patient-based assessment of symptoms.While there has been considerable work in the field over the past 10 years, this review highlights significant gaps, including a lack of evaluation of responsiveness and problematic neuropathic pain evaluation. There remains a need for consensus on the best available tool and the need to modify existing instruments to improve utility. K E Y W O R D S assessment, chemotherapy, CIPN, neuropathy, neurotoxicity, outcome measures 1 | INTRODUCTION Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prominent adverse event of cancer treatment, leading to dose reduction and premature treatment cessation, potentially affecting patient function and quality of life. The development of accurate and sensitive assessment tools for CIPN is essential to enable clinical monitoring during treatment, follow-up of long-term outcomes and measurement of toxicity in clinical trials. As with all treatment toxicities, a balanced approach between patient report, objective examination and clinician discretion is warranted. It is likely that tailored assessment strategies will be required to facilitate appropriate assessment in different contexts ranging from routine clinical screening tools to comprehensive multimodal assessments and outcome measures in clinical trials. Assessment tools which do not require specialised equipment are most accessible for routine clinical use. While common toxicity criteria (CTC) are the most commonly utilised assessment tools for a range of cancer treatment toxicities including CIPN, validated patient-reported outcome (PRO) measures provide sensitive assessment of neuropathy symptoms and significance for the patient. Composite neurological assessments containing a combination of symptom report and neurological examination findings provide another method of CIPN evaluation. Given the importance of selecting appropriate outcome measures, including in drug development and for regulatory approval, review of the properties of CIPN assessment tools is warranted.From this search, a total of 50 papers meeting inclusion criteria wer...

show abstract

Section: Discussionmentioning

confidence: 99%

Overview and critical revision of clinical assessment tools in chemotherapy‐induced peripheral neurotoxicity

Park

Alberti

Kolb

et al. 2019

J Peripheral Nervous Sys

Self Cite

View full text Add to dashboard Cite

show abstract

“…CIPN assessment is a critical issue also in the design and interpretation of neuroprotection clinical trials . The earliest clinical trials relied on the US National Cancer Institute‐Common Toxicity Criteria for Adverse Events (NCI‐CTC AE) scale to grade CIPN severity, but evidence suggests it is not the optimal endpoint …”

Section: Introductionmentioning

confidence: 99%

“…4 CIPN assessment is a critical issue also in the design and interpretation of neuroprotection clinical trials. 5 The earliest clinical trials relied on the US National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTC AE) scale to grade CIPN severity, but evidence suggests it is not the optimal endpoint. 6 Therefore, different assessment tools have been developed, such as the Total Neuropathy Score (TNS), and self-administered questionnaires, particularly the European Organization for Research and Treatment in Cancer (EORTC) QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group-Neurotoxicity (FACT-GOG Ntx).…”

mentioning

confidence: 99%

Patients' and physicians' interpretation of chemotherapy‐induced peripheral neurotoxicity

Cavaletti

Cornblath

Merkies

et al. 2019

J Peripheral Nervous Sys

Self Cite

View full text Add to dashboard Cite

To test if and how chemotherapy‐induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI‐PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation (“impossible”) generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%‐65% of patients; 76%‐78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%‐56% of them. In Group 3 strength reduction was observed in 49%‐50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.

show abstract

“…In our secondary analysis rs7349683 was not associated with PN‐related treatment disruption, probably due to the modest number of patients experiencing treatment disruption ( n = 19). Patient‐reported outcomes are more sensitive than CTCAE to changes in PN; however, for a genetic predictor to be translated into practice it must predict a clinically relevant endpoint, such as irreversible PN, PN‐induced treatment disruption, PN‐related falls or diminished quality of life.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in EPHA contributes to sensitivity to paclitaxel‐induced peripheral neuropathy

Marcath

Kidwell

Vangipuram

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims: Chemotherapy-induced peripheral neuropathy (PN) is a treatment limiting toxicity of paclitaxel. We evaluated if EPHA genetic variation (EPHA4, EPHA5, EPHA6, and EPHA8) is associated with PN sensitivity by accounting for variability in systemic paclitaxel exposure (time above threshold). Methods:Germline DNA from 60 patients with breast cancer was sequenced. PN was measured using the 8-item sensory subscale (CIPN8) of the patient-reported CIPN20. Associations for 3 genetic models were tested by incorporating genetics into previously published PN prediction models integrating measured paclitaxel exposure and cumulative treatment. Significant associations were then tested for association with PN-related treatment disruption.Results: EPHA5 rs7349683 (minor allele frequency = 0.32) was associated with increased PN sensitivity (β-coefficient = 0.39, 95% confidence interval 0.11-0.67, p = 0.007). Setting a maximum tolerable threshold of CIPN8 = 30, optimal paclitaxel exposure target is shorter for rs7349683 homozygous (11.6 h) than heterozygous (12.6 h) or wild-type (13.6 h) patients. Total number of missense variants (median = 0, range 0-2) was associated with decreased PN sensitivity (β-coefficient: −0.42, 95% confidence interval −0.72 to −0.12, P = .006). No association with treatment disruption was detected for the total number of missense variants or rs7349683. Conclusion:Isolating toxicity sensitivity by accounting for exposure is a novel approach, and rs7349683 represents a promising marker for PN sensitivity that may be used to individualize paclitaxel treatment. K E Y W O R D Sbreast cancer, genetic polymorphism, pharmacodynamics, pharmacogenomics, pharmacokinetics Principal statement: The authors confirm that the PI for this paper is D.L. Hertz and that the coinvestigator N. Lynn Henry had direct clinical responsibility for patients.

show abstract

Trial designs for chemotherapy-induced peripheral neuropathy prevention

Cited by 72 publications

References 48 publications

Overview and critical revision of clinical assessment tools in chemotherapy‐induced peripheral neurotoxicity

Overview and critical revision of clinical assessment tools in chemotherapy‐induced peripheral neurotoxicity

Patients' and physicians' interpretation of chemotherapy‐induced peripheral neurotoxicity

Genetic variation in EPHA contributes to sensitivity to paclitaxel‐induced peripheral neuropathy

Contact Info

Product

Resources

About