Prevention of Chemotherapy-Related Polyneuropathy Via Sensorimotor Exercise Training

Prevention of Chemotherapy-Related Polyneuropathy Via Sensorimotor Exercise Training

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.

Inclusion Criteria:

diagnosed with cancer and assigned to receive a chemotherapeutic regimen containing at least one of the following agents:

• a platinum analog, e.g., cisplatin, carboplatin, oxaliplatin
• a vinca alkaloid, e.g., vincristine
• a taxane, e.g., paclitaxel, docetaxel
• suramin
• thalidomide or lenalidomide
• bortezomib

Physical capability that allows the performance of the training program implemented within the experimental intervention or the control intervention arm

Exclusion Criteria:

• Known polyneuropathy of any kind or any polyneuropathic signs or symptoms at baseline
• Abnormal electroneurographic findings at baseline
• Known metastasis to the central or peripheral nervous system
• Any physical or mental handicap that would hamper the performance of the training program implemented within the intervention arms
• Family history positive for any hereditary polyneuropathy
• Known history of alcohol or illegal drug abuse or any constellation of lab values suggesting alcoholism