title: Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study.
abstract: BACKGROUND
  Peripheral neuropathy (PN) due to paclitaxel is a common dose-limiting toxicity with no effective prevention or treatment. We hypothesize that continuous-flow limb hypothermia can reduce paclitaxel-induced PN.
  
  
  METHODS
  An internally controlled pilot trial was conducted to investigate the neuroprotective effect of continuous-flow limb hypothermia in breast cancer patients receiving weekly paclitaxel. Patients underwent limb hypothermia of one limb for a duration of 3 h with every paclitaxel infusion, with the contralateral limb used as control. PN was primarily assessed using nerve conduction studies (NCSs) before the start of chemotherapy, and after 1, 3, and 6 months. Skin temperature and tolerability to hypothermia were monitored using validated scores.
  
  
  RESULTS
  Twenty patients underwent a total of 218 cycles of continuous-flow limb hypothermia at a coolant temperature of 22°C. Continuous-flow limb hypothermia achieved mean skin temperature reduction of 1.5 ± 0.7°C and was well tolerated, with no premature termination of cooling due to intolerance. Grade 3 PN occurred in 2 patients (10%), grade 2 in 2 (10%), and grade 1 in 12 (60%). Significant correlation was observed between amount of skin cooling and motor nerve amplitude preservation at 6 months (p< 0.0005). Sensory velocity and amplitude in the cooled limbs were less preserved than in the control limbs, but the difference did not attain statistical significance. One patient with a history of diabetes mellitus had significant preservation of compound muscle action potential in the cooled limb on NCS analysis.
  
  
  CONCLUSIONS
  This study suggests that continuous limb hypothermia accompanying paclitaxel infusion may reduce paclitaxel-induced PN and have therapeutic potential in select patients and warrants further investigation. The method is safe and well tolerated.
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: Raghav
authors.initials: R
authors.lastname: Sundar
authors.affiliation: Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Bandla
authors.affiliation: Singapore Institute for Neurotechnology, National University of Singapore , Singapore , Singapore.
authors.forename: Stacey Sze Hui
authors.initials: SS
authors.lastname: Tan
authors.affiliation: Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan Township, Taiwan.
authors.forename: Lun-De
authors.initials: LD
authors.lastname: Liao
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: Nesaretnam Barr
authors.initials: NB
authors.lastname: Kumarakulasinghe
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: Anand D
authors.initials: AD
authors.lastname: Jeyasekharan
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: Samuel Guan Wei
authors.initials: SG
authors.lastname: Ow
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: Jingshan
authors.initials: J
authors.lastname: Ho
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: David Shao Peng
authors.initials: DS
authors.lastname: Tan
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: Joline Si Jing
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Medicine, National University Health System , Singapore , Singapore.
authors.forename: Joy
authors.initials: J
authors.lastname: Vijayan
authors.affiliation: Neurology Diagnostic Laboratory, National University Hospital , Singapore , Singapore.
authors.forename: Aravinda K
authors.initials: AK
authors.lastname: Therimadasamy
authors.affiliation: National University Cancer Institute, National University Health System , Singapore , Singapore.
authors.forename: Zarinah
authors.initials: Z
authors.lastname: Hairom
authors.affiliation: National University Cancer Institute, National University Health System , Singapore , Singapore.
authors.forename: Emily
authors.initials: E
authors.lastname: Ang
authors.affiliation: Department of Haematology-Oncology, National University Health System , Singapore , Singapore.
authors.forename: Sally
authors.initials: S
authors.lastname: Ang
authors.affiliation: Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Nitish V
authors.initials: NV
authors.lastname: Thakor
authors.affiliation: Department of Haematology-Oncology, National University Health System, Singapore, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Soo-Chin
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore; Department of Medicine, National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Einar P V
authors.initials: EP
authors.lastname: Wilder-Smith
keywords: chemotherapy-induced peripheral neuropathy; limb hypothermia; nerve conduction; neuroprotection; paclitaxel