A randomized exploratory phase 2 study in patients with chemotherapy-related peripheral neuropathy evaluating whole-body vibration training as adjunct to an integrated program including massage, passive mobilization and physical exercises

Abstract

Background: Chemotherapy-induced polyneuropathy (CIPN) is a common toxicity after chemotherapy, immunomodulatory drugs or proteasome inhibitors, which is difficult to treat and may also have impact on quality of life. The objective of the study was to evaluate whole-body vibration (WBV) on the background of an integrated program (IP) including massage, passive mobilization and physical exercises on CIPN.

Patients and methods: In an exploratory phase-2 study patients with CIPN (NCI CTC grade 2/3) were randomized for WBV plus IP (experimental) to IP alone (standard). 15 training sessions within 15 weeks were intended. As primary endpoint we used chair-rising test (CRT) to assess physical fitness and coordination. In addition, locomotor and neurological tests and self-assessment tools were performed.

Results: A total 131 patients with CIPN were randomized (standard, n = 65; experimental, n = 66). The median age was 60 (range 24-71) years; 44 patients had haematological neoplasms and 87 solid tumors. At baseline, all patients presented with an abnormal CRT. Fifteen (standard) and 22 (experimental) patients left the program due to progression/relapse or concomitant disease. There was no significant difference in the proportion of patients with normal CRT (<10 s) at follow up between experimental (68%) and standard (56%) (p = 0.20). All patients experienced less symptoms and pain (p < 0.001) and had improved CRT (p < 0.001) over time. WBV was significantly associated with a higher reduction of time needed for CRT (p = 0.02) and significantly improved warm-detection-threshold comparing baseline to follow-up assessment (p = 0.02).

Conclusion: Whole-body vibration on the background of an IP may improve physical fitness and coordination in patients suffering from CIPN. Trial registration Retrospectively registered at http://www.iscrtn.com (ISRCTN 51361937) and http://www.clinicaltrials.gov (NCT02846844).

Keywords: Chemotherapy associated side effects; Chemotherapy related peripheral neuropathy; Integrated training program; Whole body vibration training.

Fig. 1

CONSORT diagram. This figure shows the clinical course after randomization. N = 66 patients were randomized to the experimental arm and n = 65 patients to the standard arm. N = 44 in the experimental arm and n = 50 in the standard arm reached the follow up period. R randomization, IC informed consent, n number, FU follow up, WBV whole-body vibration therapy

Fig. 2

Distribution of individual absolute time-differences in seconds between baseline and follow-up needed to complete the CRT according to randomization (black, experimental arm with whole-body vibration therapy; white, standard arm). Arrows indicate patients with normal values for completion of the CRT at follow-up. Patients with no change were marked by a ‘*’ (experimental arm) and ‘#’ (standard arm), respectively. CRT chair-rising test

Fig. 3

Distribution of individual absolute differences in degrees Celsius between baseline and completed program of the warm detection threshold (WDT) assessed with quantitative sensory testing according to randomization (black, experimental arm with whole-body vibration therapy; white, standard arm). Patients with no or very little change were marked by a ‘*’ (experimental arm) and ‘#’ (standard arm), respectively. WDT warm detection threshold

Fig. 4

Predicted times and their 95% confidence intervals for completion of the CRT according to a GEE model including assessment time points (baseline, 8th session, 15th session, follow-up), treatment arm (open circle, dashed line, without WBV; filled circle, solid line, with WBV) and initial warm detection threshold (WDT). Predictions are shown given the overall mean WDT level of 11.66. CRT chair-rising test, GEE generalized estimated equation, WBV whole-body vibration therapy, WDT warm detection threshold