Limb hypothermia for preventing paclitaxel-induced peripheral neuropathy in breast cancer patients: A pilot study

Raghav Sundar, Aishwarya Bandla, Stacey Sze Hui Tan, Lun De Liao, Nesaretnam Barr Kumarakulasinghe, Anand D. Jeyasekharan, Samuel Guan Wei Ow, Jingshan Ho, David Shao Peng Tan, Joline Si Jing Lim, Joy Vijayan, Aravinda K. Therimadasamy, Zarinah Hairom, Emily Ang, Sally Ang, Nitish V. Thakor, Soo Chin Lee, Einar P.V. Wilder-Smith

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Article number274
JournalFrontiers in Oncology
Issue numberJAN
StatePublished - Jan 10 2017


  • Chemotherapy-induced peripheral neuropathy
  • Limb hypothermia
  • Nerve conduction
  • Neuroprotection
  • Paclitaxel

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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