Chemotherapy-induced peripheral neurotoxicity (CIPN) as a side effect of chemotherapy negatively affects patients' quality of life and may lead to treatment disturbances. CIPN is frequently recorded in patients treated with alkylating platinum-based drugs, antitubulins including the taxanes and vinca alkaloids, and other drugs including suramin, thalidomide, lenalidomide and the proteasome inhibitor bortezomib, representing one of the most severe and potentially dose-limiting non-hematological toxic effects. Sufficient treatment options or preventive measures are lacking. There is evidence that physical activity strategies are able to address existing CIPN symptoms and potentially increase quality of life in affected patients. CIPN symptoms involves restrictions of sensory and sometimes motor modalities, for example, deficits in plantar perception and dysfunction of postural control and one study in type II diabetes patients also suggested that structured exercise might have a preventive potential with regard to peripheral neuropathy incidence. Based on these findings, we aim to investigate the preventive potential of a sensorimotor intervention vs. machine-based resistance training vs. usual care (wait-list control group) in a randomized controlled three-arm intervention trial among cancer patients undergoing chemotherapy with high risk for CIPN. On the basis of power calculations, the goal is to include 82 patients per intervention arm resulting in a total patients number to be enrolled of n=246. CIPN symptoms will be assessed objectively via comprehensive clinical and electrodiagnostic examinations (Total Neuropathy Scale; TNS-reduced) and subjectively via questionnaires (EORTC QLQ-CIPN20 \& FACT-GOG-Ntx, EORTC QLQ-C30). Additionally CIPN and the effectiveness of the selected interventions will be objectively evaluated by spectral analysis of Centre of Pressure (COP) variations. Further key secondary endpoints are: physical performance, sleep quality and chemotherapy compliance.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
170
National Center for Tumor Diseases
Heidelberg, Germany
Total Neuropathy Scale (TNS)
The TNS is based on symptoms, signs and basic instrumental evaluations and provides a much larger range of scoring values (0 - 40) than common oncological toxicity scales such as the National Cancer Institute (NCI) Common Toxicity Criteria (ranging from 0 - 4, cf. http://ctep.cancer.gov/forms), thus allowing the severity of CIPN to be graded more precisely. The TNS has so far been used to assess the neurotoxicity of various CIPN-relevant chemotherapeutic agents, and its results are clearly correlated with the clinically relevant results of NCI Common Toxicity Criteria, Ajani's and Eastern Cooperative Oncology Group toxicity scales, which are commonly used by oncologists.28-32 Within the PIC-Study the TNS-reduced will the primary endpoint. The TNS-reduced score excludes QST (quantitative sensory testing) vibration testing resulting in a TNS scale from 0-36.
Time frame: up to week 24 (and 3 & 6 month follow up)
Centre of Pressure (COP)
total COP displacement; mean velocity (anterior-posterior; medial-lateral) and frequency. This is just one assessement with various outcome variables
Time frame: up to week 24 (and 3 & 6 month follow up)
Strength Performance
Isometric (in four different joint angle positions) and isokinetic (at 60° angle speed) muscle capacity is measured with the Isomed 2000® diagnostic module. The protocol includes testing of representative muscles groups for upper (elbow flexors/extensors) and lower extremity (knee extensors/flexors) and is currently well established in different ongoing and finished studies in our unit.
Time frame: up to week 24
Cardiopulmonary Fitness
Maximal endurance performance (VO2peak) is measured by performing a maximal bicycle ergometer test (CPET) with a quasi-ramp protocol starting at 20 watts and increasing by 10 watts every minute until volitional exhaustion.
Time frame: up to week 24 (and 3 & 6 month follow up)
EORTC QLQ-C30
QoL will be assessed with the validated 30-item self-assessment questionnaire of the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30, version 3.0). It includes five multi-item functional scales (physical, role, emotional, cognitive, and social function), three multi-item symptom scales (fatigue, pain, nausea/vomiting), and six single items assessing further symptoms (dyspnea, insomnia, appetite loss, constipation, diarrhea) and financial difficulties.
Time frame: up to week 24 (and 3 & 6 month follow up)
EORTC QLQ-CIPN20
The EORTC QLQ-CIPN20 is a 20-item quality of life questionnaire, which has been developed to elicit patients' experience of symptoms and functional limitations related to CIPN. The CIPN20 has three subscales: a sensory, motor, and autonomic subscale. In combination with the more classical, physician-based clinical rating scales, the CIPN20 should yield a more complete picture of the nature, frequency, and severity of CIPN in a wide range of oncology patient populations. This phase IV questionnaire has been field tested in a large international clinical trial and the data are currently being analyzed.
Time frame: prior to each Chemotherapy cycle within the first 24 weeks (and 3 & 6 month follow up)
FACT-GOG-Ntx
The FACT-GOG-Ntx is an eleven-item scale that evaluates symptoms and concerns associated specifically with chemotherapy-induced peripheral neuropathy. The questionnaire has been validated, ranges from zero to 44 with higher scores indicating increased CIPN symptoms and has been used in various clinical trials.
Time frame: prior to each Chemotherapy cycle within the first 24 weeks (and 3 & 6 month follow up)
Multidimensional Fatigue Inventory (MFI)
Fatigue will be assessed with the Multidimensional Fatigue Inventory (MFI) which is a 20-item, multidimensional self-assessment questionnaire that has been validated for a German-speaking population. It covers five different dimensions of fatigue (general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue). Scores are derived by summing the answers (five-stage scale) of the appropriate items. The MFI has been used to assess fatigue in a variety of cancer patient studies, and psychometric properties of this instrument have been classified as satisfying or good.
Time frame: up to week 24 (and 3 & 6 month follow up)
Pittsburgh Sleep Quality Index (PSQI)
Sleep quality and sleep problems will be assessed with the validated and frequently used Pittsburgh Sleep Quality Index
Time frame: up to week 24 (and 3 & 6 month follow up)
Short QUestionnaire to ASsess Health-enhancing Physical Activity
Physical activity behavior (PA) in the domains of commuting activity, leisure time activities such as cycling, walking, and sports, household and occupational activity will be assessed via a standardized and validated questionnaire, the Short QUestionnaire to ASsess Health-enhancing PA (SQUASH) which has the advantage that it is short and easy to complete.
Time frame: up to week 24 (and 3 & 6 month follow up)
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