A randomized phase-3 study in patients with chemotherapyinduced sensorimotor polyneuropathy evaluating an integrated program including massage, structured kinesthetic three-dimensional mobilization, physical exercises with or without whole-body vibration training

Background: Peripheral sensorimotor polyneuropathy (PNP) frequent results from toxicity of chemotherapy and single agent IMiDs or proteasom inhibitors. Chemotherapy‐induced PNP (ciPNP) is characterized by an enormous interference with daily activity of life because of pain, severe disturbance of fine motor skills and insomnia. The therapeutic benefit of medical treatment is uncertain. Methods: In a phase‐III study patients with ciPNP grade 2/3 according to NCI CTC were randomized for an integrated program including massage, kinesthetic three‐dimensional mobilization, and physical exercises with or without vibration platform training. All patients were intended to receive 15 sessions in a time period of 12 to 15 weeks. Patients were evaluated before, during and after treatment using locomotoric‐ and sensory tests, neurological evaluation and self‐assessment. Results: A total of 131 patients with ciPNP were randomized either into the standard arm (n = 65, integrated program only) or the experimental arm (n = 66, integrated program with vibration platform training). The median age was 60 years (range 24‐71years); n = 44 patients had haematological neoplasms (n = 19 multiple myelomas, n = 18 lymphomas, n = 7 leukemias) and n = 87 solide tumors (n = 27 colorectal, n = 8 lung, n = 8 oesophageal/gastric, n = 25 breast/ovarian, n = 19 others). All patients had prior chemotherapy and n = 46 had additional radiotherapy. At baseline, according to the visual analog scale (best, 0‐10, worst) polyneuropathy‐ symptoms including pain were predominantly present in toes (median 8.1) and fingers (median 6.4). During the intervention time period n = 19 (standard) and n = 32 (experimental) patients left the program due to progression/relapse, concomitant disease or death. Overall, the patients experienced marked improvement with significantly less symptoms and pain (p < 0.001), better physical fitness and coordination (Esslinger‐fitness‐ index, p = 0.006; chair‐rising‐test p < 0.001), and better results in quantitative sensory testing (QST) with thermal perception, blunt pressure, mechanical pain and vibration thresholds. Significant differences were noted in favor of the vibration platform training in daily walking distance within the first sessions (p < 0.001) and overall in improved thermal QST perception (p = 0.03). Conclusions: The treatment of ciPNP with an integrated program had a significant and clinically extremely relevant beneficial impact on symptom relieve, physical fitness and sensory function.