Original Title: État des connaissances - Cryothérapie et prévention des neuropathies périphériques induites par l’administration des taxanes

Authors' objectives: Many solid tumours are treated with chemotherapy drugs, including those in the taxane family. These drugs can have significant adverse effects, especially symptoms of chemotherapy-induced peripheral neuropathy (CIPN). These symptoms manifest as sensory and motor disorders and as pain in the upper and lower limbs. The symptoms are associated with poorer quality of life. The incidence of peripheral neuropathy symptoms ranges from 30% to 70%, depending on the chemotherapy drug administered, and no prophylactic medical treatment has been shown to be effective in preventing or treating them. Some cancer care teams use non-pharmacological measures to prevent the neurotoxic effects of chemotherapy. One of the methods used, cryotherapy, involves cooling the hands and feet with frozen gloves and socks during chemotherapy infusions, particularly taxanes. The goal of this measure is to reduce the amount of blood flow to the extremities and thus prevent neurotoxicity. The assistant director of the Québec Cancer Program (PQC) and the Direction générale des affaires universitaires, médicales, infirmières et pharmaceutiques (DGAUMIP) of the Ministère de la Santé et des Services sociaux (MSSS) asked the Institut national d'excellence en santé et en services sociaux (INESSS) to produce a state-of-knowledge report and to indicate the learned societies’ respective positions regarding the efficacy and safety of cryotherapy for the prevention of taxane-induced peripheral neuropathy.

Authors' results and conclusions: RESULTS: (#1 CONTEXT AND HEALTH NEED): Chemotherapy-induced peripheral neurotoxicity is a common phenomenon affecting 30% to 70% of patients receiving chemotherapy. It manifests as paresthesia and sometimes motor disorders (manipulative dexterity problems, cramps and muscle weakness), which can be significant. Some patients can experience long-term sequelae. The severity of these symptoms can have a considerable impact on the quality of life of patients receiving chemotherapy, including taxanes. It can even lead to a reduction in the required chemotherapy doses or to a delay in or the discontinuation of cancer treatment. (#2 NEUROTOXICITY AND CRYOTHERAPY): Paclitaxel and docetaxel are two drugs in the taxane family with a high neurotoxic potential. They are often administered to treat many types of solid tumours. • The use of cryotherapy to prevent neurotoxicity is inspired by the positive results obtained with the use of cold caps to prevent alopecia after chemotherapies treatment and with the use of cold (frozen gloves and socks) to reduce nail toxicity. Based on this same principle, teams of clinicians in several countries are using devices, such as frozen gloves and socks, placed on the extremities during cancer treatment cycles to prevent the toxic effects of chemotherapy on the peripheral nerves. (#3 ASSESSMENT OF THE LEVEL OF SCIENTIFIC EVIDENCE): There are few publications of good methodological quality on the subject. Eleven were selected, five of which were randomized and unblinded and involved small numbers of patients. • The objectives of cryotherapy were poorly achieved in the studies identified, and the clinical significance of the scientific evidence is uncertain. • The reported studies have numerous methodological limitations that can lead to a very high risk of bias, which makes it difficult to interpret the results: a lack of consistency, credibility and reliability. (#4 EFFICACY AND SAFETY): The available data, which are from studies of low methodological quality, do not permit any conclusions regarding: – The efficacy of cryotherapy in preventing chemotherapy-induced peripheral neuropathy; – The safety of cryotherapy or patients’ tolerance of this preventive treatment, which requires exposure to cold, sometimes for the entire duration of administration. Otherwise, the adverse effects associated with cryotherapy appear to be infrequent and mild in the few studies that have assessed them. Although no studies reported any cases of frostbite, cold intolerance was reported in six of eleven studies and caused several cases of attrition. No cases of cryotherapy discontinuation were observed in the other studies. • Most authors mention that more methodologically robust studies are needed to properly evaluate the efficacy and safety of cryotherapy for the prevention of taxane-induced peripheral neuropathy (PN).

Authors' recommendations: The clinicians and experts consulted recognize: – The important need to prevent symptoms of taxane-induced neuropathy; – The lack of conclusive scientific evidence for the efficacy of cryotherapy due to the limited number of studies available and their low methodological quality; – The need for better-quality studies before a position can be taken on the matter. • Although the results observed are mixed, some experts feel that cryotherapy is a promising preventive treatment, since it has few or no major adverse effects and can be stopped at any time without compromising the effectiveness of the cancer treatment.

Authors' methods: For the purpose of this mandate, a search of the scientific and grey literature was conducted, targeting systematic reviews, with or without meta-analysis, primary studies (randomized or non-randomized clinical trials), cohort studies, and clinical practice guidelines. Conference abstracts and narrative studies were excluded. The selected findings were presented and discussed with the Comité d'évolution des pratiques en oncologie (CEPO) and were then reviewed by external reviewers.

Authors' identified further research: The only clinical practice guideline found states that no recommendation can be made regarding the use of various pharmacological and non-pharmacological options for preventing peripheral neuropathy, including cryotherapy, because of the low methodological quality of the selected studies. However, the authors of the guideline add that, while this has not been proven, the available data do suggest that cryotherapy may partially prevent neuropathy symptoms and that its use appears to be reasonably safe. The advisability of updating this state-of-knowledge report will be assessed and determined on the basis of the results of certain ongoing clinical trials on this topic. The results of these trials are expected to be published starting in 2023-2024. An update may be necessary if there is a significant amount of new available data for any of the aspects examined in this state-of-knowledge report.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/cryotherapie-et-prevention-des-neuropathies-peripheriques-induites-par-ladministration-des-taxanes.html

Year Published: 2023

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/cryotherapie-et-prevention-des-neuropathies-peripheriques-induites-par-ladministration-des-taxanes.html

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec