CI‐PERINOMS: chemotherapy‐induced peripheral neuropathy outcome measures study

Chemotherapy-induced peripheral neuropathy (CIPN) is a major and potentially dose-limiting adverse event of several chemotherapeutic agents (Windebank and Grisold, 2008). CIPN is characterized by distal symmetrical numbness, tingling, paresthesias, dysesthesias, pain and/or weakness, which significantly affect functionality and quality of life (Aaronson, 1998). The incidence of CIPN may be as high as 100% in treated patients, depending on dose and dose-intensity of the chemotherapeutic regimen. The neurotoxic side effects may be permanent, and treatment is usually difficult. Neuroprotective agents that would either prevent or ameliorate CIPN are currently under investigation (Cavaletti and Marmiroli, 2006; Albers et al., 2007). However, before studying these agents in clinical trials, it is crucial to be able to assess CIPN in a simple, valid, and reproducible way in accordance with postulated international guidelines (Hobart et al., 1996; Merkies and Lauria, 2006). Although several scales have been used by oncologists and neurologists, grading CIPN is still an unsolved issue (Postma and Heimans, 2000; Cavaletti et al., 2007). Moreover, most of the scales have not undergone rigorous clinimetric evaluation and analysis, which are nowadays essential requirements for any proposed clinical trial (van Nes et al., 2008). The CI-PERINOMS: Chemotherapy Induced-Peripheral Neuropathy Outcome Measures Study protocol was developed by experienced neurologists to identify the best method(s) to assess and monitor CIPN (Cavaletti, 2008). After a consensus meeting held in Pomezia (Italy, June 22, 2007) where the CI-PERINOMS protocol was developed, and after local Institutional Review Board (IRB) approval, neurologists and oncologists from 21 centers in the United States and the European Union, selected based on their capability to perform the comprehensive testing and to recruit the types of subjects appropriate for this study, are now assessing the validity and reproducibility of the selected outcome measures. The primary endpoint of the study is to determine the validity and reproducibility of the proposed outcome measures in CIPN. Secondary objectives are the development of an overall disability sum-score (ODSS) specific to CIPN and the development of a responsiveness study based on the results of the study. According to the protocol, the clinimetric assessment of CIPN will be performed at two levels: a Core and an Extended study. The Core study has been designed to be feasible in both Oncology and Neurology departments, whereas the Extended study requires a neurophysiological examination. As part of the Core study, all the subjects will be examined with the following scales: TNSc = Total Neuropathy Score, clinical version (Cornblath et al., 1999; Cavaletti et al., 2003; 2006); VAS = visual analog pain scale (Maxwell, 1978); PI-NRS = 11-point-pain intensity numerical scale (Farrar et al., 2001); C-ODSS = calibrated-overall disability sumscore (Merkies et al., 2002); NCI-CTC 3.0 = National Cancer Institute-Common Toxicity Criteria, version 3.0; QLQ-CIPN20 EORTC = quality of life questionnaire for CIPN and QLQ-C30 = EORTC 30item questionnaire for cancer patients (Postma et al., 2005); QoL-PS = quality of life personal score. The Extended study, performed in a subgroup of patients, will consist of the Core measures plus Sensory examination by modified INCAT sensory sumscore (mISS) and nerve conduction studies. For the assessment of inter-observer and intraobserver and test–retest studies, two investigators in each participating center will evaluate study subjects, applying the selected impairment and activity limitation scales. Electrophysiological studies will be performed only once at entry. Subjects will be examined at two different occasions at the outpatient clinics. During the first visit, the two examiners will perform their scores independently and consecutively within 2 hours (interobserver measures). Within 1–3 weeks, the subject will return for a second visit and both investigators will re-examine the subject (intra-observer values) without having access to previous results. The outcome