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

Aishwarya Bandla, Stacey Tan, Nesaretnam Barr Kumarakulasinghe, Yiqing Huang, Sally Ang, Gayathiri Magarajah, Zarinah Hairom, Joline Si Jing Lim, Alvin Wong, Gloria Chan, Natalie Ngoi, Emily Ang, Yee Mei Lee, Amanda Chan, Soo Chin Lee, Nitish Thakor, Einar Wilder-Smith, Raghav Sundar

Research output: Contribution to journalArticle

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 (NCSpre), after completion (NCSpost) and 3 months post-chemotherapy (NCS3m). 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 NCS3m in subjects who underwent cryocompression, compared to the controls who showed significant deterioration (NCS3m cryocompression vs. NCS3m control: ankle stimulation: 8.1 ± 21.4%, p = 0.004; below fibula head stimulation: 12.7 ± 25.6%, p = 0.0008; above fibula head stimulation: 9.4 ± 24.3%, p = 0.002). Cryocompression did not significantly affect taxane-induced changes in sensory nerve amplitudes. Conclusion: When compared to continuous-flow cooling, cryocompression permitted delivery of lower temperatures with similar tolerability. The lower skin surface temperatures achieved potentially lead to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are required to validate these findings.

Original languageEnglish (US)
JournalSupportive Care in Cancer
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Peripheral Nervous System Diseases
Hypothermia
Extremities
Safety
Drug Therapy
Skin Temperature
Fibula
Neural Conduction
Paclitaxel
Temperature
Frostbite
taxane
Pressure
Ankle
Equipment and Supplies
Incidence

Keywords

  • Chemotherapy-induced peripheral neuropathy
  • Cryocompression
  • Cryotherapy
  • Nerve conduction
  • Paclitaxel

ASJC Scopus subject areas

  • Oncology

Cite this

Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy. / Bandla, Aishwarya; Tan, Stacey; Kumarakulasinghe, Nesaretnam Barr; Huang, Yiqing; Ang, Sally; Magarajah, Gayathiri; Hairom, Zarinah; Lim, Joline Si Jing; Wong, Alvin; Chan, Gloria; Ngoi, Natalie; Ang, Emily; Lee, Yee Mei; Chan, Amanda; Lee, Soo Chin; Thakor, Nitish; Wilder-Smith, Einar; Sundar, Raghav.

In: Supportive Care in Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Bandla, A, Tan, S, Kumarakulasinghe, NB, Huang, Y, Ang, S, Magarajah, G, Hairom, Z, Lim, JSJ, Wong, A, Chan, G, Ngoi, N, Ang, E, Lee, YM, Chan, A, Lee, SC, Thakor, N, Wilder-Smith, E & Sundar, R 2019, 'Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy', Supportive Care in Cancer. https://doi.org/10.1007/s00520-019-05177-2
Bandla, Aishwarya ; Tan, Stacey ; Kumarakulasinghe, Nesaretnam Barr ; Huang, Yiqing ; Ang, Sally ; Magarajah, Gayathiri ; Hairom, Zarinah ; Lim, Joline Si Jing ; Wong, Alvin ; Chan, Gloria ; Ngoi, Natalie ; Ang, Emily ; Lee, Yee Mei ; Chan, Amanda ; Lee, Soo Chin ; Thakor, Nitish ; Wilder-Smith, Einar ; Sundar, Raghav. / Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy. In: Supportive Care in Cancer. 2019.
@article{42519c474e114b1282b0d07a4d6795f2,
title = "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 (NCSpre), after completion (NCSpost) and 3 months post-chemotherapy (NCS3m). 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 NCS3m in subjects who underwent cryocompression, compared to the controls who showed significant deterioration (NCS3m cryocompression vs. NCS3m control: ankle stimulation: 8.1 ± 21.4{\%}, p = 0.004; below fibula head stimulation: 12.7 ± 25.6{\%}, p = 0.0008; above fibula head stimulation: 9.4 ± 24.3{\%}, p = 0.002). Cryocompression did not significantly affect taxane-induced changes in sensory nerve amplitudes. Conclusion: When compared to continuous-flow cooling, cryocompression permitted delivery of lower temperatures with similar tolerability. The lower skin surface temperatures achieved potentially lead to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are required to validate these findings.",
keywords = "Chemotherapy-induced peripheral neuropathy, Cryocompression, Cryotherapy, Nerve conduction, Paclitaxel",
author = "Aishwarya Bandla and Stacey Tan and Kumarakulasinghe, {Nesaretnam Barr} and Yiqing Huang and Sally Ang and Gayathiri Magarajah and Zarinah Hairom and Lim, {Joline Si Jing} and Alvin Wong and Gloria Chan and Natalie Ngoi and Emily Ang and Lee, {Yee Mei} and Amanda Chan and Lee, {Soo Chin} and Nitish Thakor and Einar Wilder-Smith and Raghav Sundar",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00520-019-05177-2",
language = "English (US)",
journal = "Supportive Care in Cancer",
issn = "0941-4355",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy

AU - Bandla, Aishwarya

AU - Tan, Stacey

AU - Kumarakulasinghe, Nesaretnam Barr

AU - Huang, Yiqing

AU - Ang, Sally

AU - Magarajah, Gayathiri

AU - Hairom, Zarinah

AU - Lim, Joline Si Jing

AU - Wong, Alvin

AU - Chan, Gloria

AU - Ngoi, Natalie

AU - Ang, Emily

AU - Lee, Yee Mei

AU - Chan, Amanda

AU - Lee, Soo Chin

AU - Thakor, Nitish

AU - Wilder-Smith, Einar

AU - Sundar, Raghav

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 (NCSpre), after completion (NCSpost) and 3 months post-chemotherapy (NCS3m). 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 NCS3m in subjects who underwent cryocompression, compared to the controls who showed significant deterioration (NCS3m cryocompression vs. NCS3m control: ankle stimulation: 8.1 ± 21.4%, p = 0.004; below fibula head stimulation: 12.7 ± 25.6%, p = 0.0008; above fibula head stimulation: 9.4 ± 24.3%, p = 0.002). Cryocompression did not significantly affect taxane-induced changes in sensory nerve amplitudes. Conclusion: When compared to continuous-flow cooling, cryocompression permitted delivery of lower temperatures with similar tolerability. The lower skin surface temperatures achieved potentially lead to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are required to validate these findings.

AB - 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 (NCSpre), after completion (NCSpost) and 3 months post-chemotherapy (NCS3m). 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 NCS3m in subjects who underwent cryocompression, compared to the controls who showed significant deterioration (NCS3m cryocompression vs. NCS3m control: ankle stimulation: 8.1 ± 21.4%, p = 0.004; below fibula head stimulation: 12.7 ± 25.6%, p = 0.0008; above fibula head stimulation: 9.4 ± 24.3%, p = 0.002). Cryocompression did not significantly affect taxane-induced changes in sensory nerve amplitudes. Conclusion: When compared to continuous-flow cooling, cryocompression permitted delivery of lower temperatures with similar tolerability. The lower skin surface temperatures achieved potentially lead to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are required to validate these findings.

KW - Chemotherapy-induced peripheral neuropathy

KW - Cryocompression

KW - Cryotherapy

KW - Nerve conduction

KW - Paclitaxel

UR - http://www.scopus.com/inward/record.url?scp=85076309347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076309347&partnerID=8YFLogxK

U2 - 10.1007/s00520-019-05177-2

DO - 10.1007/s00520-019-05177-2

M3 - Article

C2 - 31811482

AN - SCOPUS:85076309347

JO - Supportive Care in Cancer

JF - Supportive Care in Cancer

SN - 0941-4355

ER -