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One of the two studies that applied a relatively lesser amount of cooling as defined in this review achieved statistically significant benefits in the severity of peripheral neuropathy ( Tsuyuki et al., 2016). This prospective, self-controlled study included 42 breast cancer patients who received compression therapy with two surgical gloves sized one size too small worn on the dominant hand, which resulted in a decrease in fingertip temperature on the intervention side. Subjects received nab-paclitaxel every 3 weeks for four cycles. Outcomes were measured using the CTCAE and the PNQ and were recorded at baseline, before each treatment cycle, and 1 week after nab-paclitaxel was administered. CTCAE results demonstrated a decrease in the incidence of ≥ grade 2 peripheral neuropathy on the intervention side ( p< .0001). The occurrence of ≥ grade 2 sensory neurotoxicity decreased from 76.1% to 21.4%, and that of motor neurotoxicity decreased from 57.1% to 26.2%. Patient Neuropathy Questionnaire results demonstrated significantly lower grades of peripheral neuropathy on the intervention side ( p< .0001). Chemotherapy-induced peripheral neuropathy may be associated with decreased quality of life, reduced functional abilities, and may prevent patients from returning to work ( Miltenburg & Boogerd, 2014; Mols, Beijers, Vreugdenhil, & van de Poll-Franse, 2014; Tofthagen, 2010; Zanville et al., 2016). Functional limitations of CIPN relate to hand pain, hand numbness affecting fine motor skills, and foot pain and numbness, which may cause difficulty walking ( Bhatnagar et al., 2014; Zanville et al., 2016). Symptoms and severity of CIPN are also associated with an increased risk of falls ( Tofthagen, Overcash, & Kip, 2012). Symptoms of CIPN contribute to feelings of depression and loss of purpose when patients lose the ability to engage in activities they enjoy ( Tofthagen, 2010). The duration of CIPN symptoms ranges from months to years following treatment and may be permanent ( Miltenburg & Boogerd, 2014).

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National Cancer Institute’s Common Toxicity Criteria, version 2.0, translated into Danish, including sensory neuropathy symptoms Bandla A., Sundar R., Liao L. D., Sze Hui Tan S., Lee S. C., Thakor N. V., & Wilder-Smith E. P. (2016). Hypothermia for preventing chemotherapy-induced neuropathy - a pilot study on safety and tolerability in healthy controls. Acta Oncologica, 55( 4), 430–436. 10.3109/0284186X.2015.1075664 [ PubMed] [ CrossRef] [ Google Scholar] Christodoulou C., Tsakalos G., Galani E., & Skarlos D. V. (2006). Scalp metastases and scalp cooling for chemotherapy-induced alopecia prevention. Annals of Oncology, 17( 2), 350 Tsuyuki S., Senda N., Kanng Y., Yamaguchi A., Yoshibayashi H., Kikawa Y.,...Inamoto T. (2016). Evaluation of the effect of compression therapy using surgical gloves on nanoparticle albumin-bound paclitaxel-induced peripheral neuropathy: A phase II multicenter study by the Kamigata Breast Cancer Study Group. Breast Cancer Research in Treatment, 160( 1), 61–67. 10.1007/s10549-016-3977-7 [ PubMed] [ CrossRef] [ Google Scholar]Komen M. M., Smorenburg C. H., van den Hurk C. J., & Nortier J. W. (2013). Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia. Oncologist, 18( 7), 885–891. https://dx.doi.org/10.1634%2Ftheoncologist.2012-0332 [ PMC free article] [ PubMed] [ Google Scholar] Tofthagen C. (2010). Patient perceptions associated with chemotherapy-induced peripheral neuropathy. Clinical Journal of Oncology Nursing, 14( 3), E22–E28. 10.1188/10.CJON.E22-E28 [ PubMed] [ CrossRef] [ Google Scholar] Hanai A., Ishiguro H., Sozu T., Tsuda M., Yano I., Nakagawa T.,...Tsuboyama T. (2018). Effects of cryotherapy on objective and subjective symptoms of paclitaxel-induced neuropathy: Prospective self-controlled trial. Journal of the National Cancer Institute, 110( 2), 141–148. 10.1093/jnci/djx178 [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar] Determine whether limb hypothermia is protective against paclitaxel-induced peripheral neuropathy and assess safety and tolerability

The Impact of Peripheral Cooling on Chemotherapy-Induced

Reduced incidence of ≥ grade 2 peripheral neuropathy in the intervention group (5.0%–9.1%) vs. the control group (22.5%–35.8%); p< .05 at the fourth cycle and p< .01 after the fifth cycle No significant difference in Neuropathic Pain Symptom Inventory scores for symptoms in hands ( p> .15) or feet ( p> .30); no significant difference in quantitative sensory testing results ( p> .15); and pain severity using the Brief Pain Inventory was increased for all measures across time Symptoms assessed at baseline and before every cycle of paclitaxel administration during outpatient care

Compound motor action potential amplitudes of motor nerves more preserved at 3 months post treatment. Did not achieve statistical significance. Extensor digitorum brevis compound motor action potential amplitudes more preserved on intervention side below fibula head ( p = .07) and above fibula head ( p = .10). The single study in this review that achieved fingertip cooling by compression with surgical gloves demonstrated statistically significant benefits with the intervention ( Tsuyuki et al., 2016). It should be noted that it is uncertain to what degree the observed benefit in this study is attributed to a decrease in circulation at target tissues compared with a resulting decrease in temperature. Additional studies are needed to further assess the validity of the findings in the Tsuyuki study and to discern benefit from compression compared with direct cooling. Fingertip cooling by compression offers a promising area for further study given its low cost, ease of application, and seemingly good tolerability. CTCAE results: Decrease in the incidence of ≥ grade 2 peripheral neuropathy in the intervention side ( p< .0001). The occurrence of ≥ grade 2 sensory neurotoxicity decreased from 76.1% to 21.4%, and that of motor neurotoxicity decreased from 57.1% to 26.2%

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Tofthagen C., Overcash J., & Kip K. (2012). Falls in persons with chemotherapy-induced peripheral neuropathy. Supportive Care in Cancer, 20( 3), 583–589. 10.1007/s00520-011-1127-7 [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar] Similar benefit after subsequent chemo cycles (odds ratio: 0.59; 95% CI = 0.46–0.76, p< .0001), although analysis of impact of preexisting peripheral neuropathy not performed in statistics for late peripheral neuropathy group de Lemos M. L., & Walisser S. (2005). Management of extravasation of oxaliplatin. Journal of Oncology Pharmacy Practice, 11( 4), 159–162. 10.1191/1078155205jp165oa [ PubMed] [ CrossRef] [ Google Scholar] No statistically significant preservation of hand or foot cold sense, vibration perception, electrophysiological measurementsShah A., Hoffman E. M., Mauermann M. L., Loprinzi C. L., Windebank A. J., Klein C. J., & Staff N. P. (2018). Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort. Journal of Neurology, Neurosurgery, and Psychiatry, 89( 6), 636–641. 10.1136/jnnp-2017-317215 [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar]