Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy

Abstract

Purpose Severe peripheral neuropathy is a common dose-limiting toxicity of taxane chemotherapy, with no effective treatment. Frozen gloves have shown to reduce the severity of neuropathy in several studies but comes with the incidence of undesired side effects such as cold intolerance and frostbite in extreme cases. A device with thermoregulatory features which can safely deliver tolerable amounts of cooling while ensuring efficacy is required to overcome the deficiencies of frozen gloves. The role of continuous-flow cooling in prevention of neurotoxicity caused by paclitaxel has been previously described. This study hypothesized that cryocompression (addition of dynamic pressure to cooling) may allow for delivery of lower temperatures with similar tolerance and potentially improve efficacy. Method A proof-of-concept study was conducted in cancer patients receiving taxane chemotherapy. Each subject underwent four-limb cryocompression with each chemotherapy infusion (three hours) for a maximum of 12 cycles. Cryocompression was administered at 16°C and cyclic pressure (5-15 mmHg). Skin surface temperature and tolerance scores were recorded. Neuropathy was assessed using clinician-graded peripheral sensory neuropathy scores, total neuropathy score (TNS) and nerve conduction studies (NCS) conducted before (NCS pre), after completion (NCS post) and 3 months post-chemotherapy (NCS 3m). Results were retrospectively compared with patients who underwent paclitaxel chemotherapy along with continuous-flow cooling and controls with no hypothermia. Results In total, 13 patients underwent 142 cycles of cryocompression concomitant with chemotherapy. Limb hypothermia was well tolerated, and only 1 out of 13 patients required an intra-cycle temperature increase, with no early termination of cryocompression in any subject. Mean skin temperature reduction of 3.8 ± 1.7°C was achieved. Cryocompression demonstrated significantly greater skin temperature reductions compared to continuous-flow cooling and control (p < 0.0001). None of the patients experienced severe neuropathy (clinician-assessed neuropathy scores of grade 2 or higher). NCS analysis showed preservation of motor amplitudes at NCS 3m in subjects who underwent cryocompression, compared to the controls who showed Electronic supplementary material The online version of this article (

Cryotherapy for the prevention of chemotherapy-induced peripheral neuropathy: A systematic review

“…20 Another trial assessing nerve conduction demonstrated that cryocompression preserved motor amplitudes at 3 months. 26 Conversely, several studies included in this review reported that cryotherapy was not beneficial for the prevention of CIPN. 16,18,22,24 Both Beijers et al and Ruddy et al indicated no important differences in change of EORTC QLQ-CIPN20 scores.…”

“…20 Another trial assessing nerve conduction demonstrated that cryocompression preserved motor amplitudes at 3 months. 26…”

“…Eleven studies were included for a total of 2,356 patients. The majority of the trials were conducted in patients receiving treatment with paclitaxel 16,18,19,[21][22][23]25,26 or docetaxel 17,26 and one trial assessed cancer patients who were receiving paclitaxel, docetaxel, or oxaliplatin. 24 Overall, the efficacy of cryotherapy for the prevention of CIPN was mixed, with approximately half of the included studies demonstrating significant improvement in at least one endpoint.…”

“…A total of 11 studies were included in the final review (Table 1). [16][17][18][19][20][21][22][23][24][25][26] Literature review The average age of patients in the cryotherapy group was 53. At the end of 12 weeks, there was no difference in the AUC of the CIPN-20 scores between the two groups.…”

“…For safety outcomes, 1 (8%) patient in the cryocompression required an intra-cycle temperature increase. 26…”