AUTHOR=Sundar Raghav , Bandla Aishwarya , Tan Stacey Sze Hui , Liao Lun-De , Kumarakulasinghe Nesaretnam Barr , Jeyasekharan Anand D. , Ow Samuel Guan Wei , Ho Jingshan , Tan David Shao Peng , Lim Joline Si Jing , Vijayan Joy , Therimadasamy Aravinda K. , Hairom Zarinah , Ang Emily , Ang Sally , Thakor Nitish V. , Lee Soo-Chin , Wilder-Smith Einar P. V. TITLE=Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study JOURNAL=Frontiers in Oncology VOLUME=6 YEAR=2017 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2016.00274 DOI=10.3389/fonc.2016.00274 ISSN=2234-943X 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.

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.