Effect of cryotherapy on dose of adjuvant paclitaxel in early-stage breast cancer

Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel. Though no pharmacological agents have been identified to prevent CIPN, cryotherapy with frozen gloves and socks may reduce the risk of developing CIPN and thereby increase the likelihood of patients completing the planned dose of paclitaxel.

Patients and methods

Among women with early-stage breast cancer who received at least one cycle of paclitaxel, 119 were included in the 2016 cohort who received cryotherapy when they developed symptoms of CIPN, and 96 patients in the 2017 cohort who received prophylactic cryotherapy. From electronic patient records, data were abstracted on dates and doses of adjuvant paclitaxel, dose reductions, cycle delays, symptoms of CIPN, and whether and when frozen gloves and socks were used. The outcome was the proportion of patients completing the planned 720 mg/m2 of paclitaxel cumulated over nine cycles. The hazard ratio (HR) of a dose-limiting event due to CIPN was estimated in a Cox proportional hazards model.

Results

In the 2016 cohort, cryotherapy was needed due to symptoms of CIPN in 54 (45%) patients. Significantly, more patients, 77% in the 2017 cohort, completed the planned dose of 720 mg/m² compared with 64% in the 2016 cohort, p = 0.017. The HR of a dose reduction or cessation due to CIPN, adjusted for age and HER-2 status, was 0.50 (95% confidence interval 0.30–0.84), p = 0.009, for the 2017 cohort compared with the 2016 cohort.

Conclusions

The results of this study suggest that prophylactic cryotherapy may reduce the risk of a dose-limiting event due to CIPN and increase the proportion of patients completing the planned dose of paclitaxel in adjuvant treatment of early-stage breast cancer. Despite this, CIPN remains to be an important dose-limiting toxicity of paclitaxel.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

Data availability

I have full control of all primary data, and I agree to allow the journal to review the data if requested.

References

  1. 1.

    Hershman DL, Lacchetti C, Loprinzi CL (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline summary. J Oncol Pract. 10(6):e421–e4e4

    Article  Google Scholar 

  2. 2.

    Eckhoff L, Knoop AS, Jensen MB, Ejlertsen B, Ewertz M (2013) Risk of docetaxel-induced peripheral neuropathy among 1,725 Danish patients with early stage breast cancer. Breast Cancer Res Treat 142(1):109–118

    CAS  Article  Google Scholar 

  3. 3.

    Hanai A, Ishiguro H, Sozu T, Tsuda M, Yano I, Nakagawa T, Imai S, Hamabe Y, Toi M, Arai H, Tsuboyama T (2018) Effects of cryotherapy on objective and subjective symptoms of paclitaxel-induced neuropathy: prospective self-controlled trial. J Natl Cancer Inst 110(2):141–148

    CAS  Article  Google Scholar 

  4. 4.

    Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T et al (2015) Long-term follow-up of the e1199 phase iii trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol 33(21):2353–2360

    CAS  Article  Google Scholar 

  5. 5.

    Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Hojris I et al (2017) Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol 35(23):2639–2646

    CAS  Article  Google Scholar 

  6. 6.

    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42(2):377–381

    Article  Google Scholar 

  7. 7.

    StataCorp (2017) Stata Statistical Software: Release 15. TX. StataCorp LLC, College Station

    Google Scholar 

  8. 8.

    R Core Team (2019) R: a language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria (https://www.r-project.org/)

  9. 9.

    Sato J, Mori M, Nihei S, Kumagai M, Takeuchi S, Kashiwaba M et al (2016) The effectiveness of regional cooling for paclitaxel-induced peripheral neuropathy. J Pharm Health Care Sci 2:33

    Article  Google Scholar 

  10. 10.

    Sundar R, Bandla A, Tan SS, Liao LD, Kumarakulasinghe NB, Jeyasekharan AD et al (2016) Limb hypothermia for preventing paclitaxel-induced peripheral neuropathy in breast cancer patients: a pilot study. Front Oncol 6:274

    PubMed  Google Scholar 

  11. 11.

    Ruddy KJ, Le-Rademacher J, Lacouture ME, Wilkinson M, Onitilo AA, Vander Woude AC et al (2019) Randomized controlled trial of cryotherapy to prevent paclitaxel-induced peripheral neuropathy (RU221511I); an ACCRU trial. Breast 48:89–97

    Article  Google Scholar 

  12. 12.

    Kadakia KC, Rozell SA, Butala AA, Loprinzi CL (2014) Supportive cryotherapy: a review from head to toe. J Pain Symptom Manag 47(6):1100–1115

    Article  Google Scholar 

  13. 13.

    Park SB, Goldstein D, Krishnan AV, Lin CS, Friedlander ML, Cassidy J et al (2013) Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin 63(6):419–437

    Article  Google Scholar 

  14. 14.

    Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet 2019 393(10179):1440-52

  15. 15.

    Chirivella I, Bermejo B, Insa A, Perez-Fidalgo A, Magro A, Rosello S et al (2009) Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients. Breast Cancer Res Treat 114(3):479–484

    CAS  Article  Google Scholar 

  16. 16.

    Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L (2004) Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol 22(11):2061–2068

    CAS  Article  Google Scholar 

  17. 17.

    Schneider BP, Zhao F, Wang M, Stearns V, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE, Sparano JA (2012) Neuropathy is not associated with clinical outcomes in patients receiving adjuvant taxane-containing therapy for operable breast cancer. J Clin Oncol 30(25):3051–3057

    CAS  Article  Google Scholar 

  18. 18.

    Speck RM, Sammel MD, Farrar JT, Hennessy S, Mao JJ, Stineman MG et al (2013) Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. J Oncol Pract 9(5):e234–e240

    Article  Google Scholar 

  19. 19.

    Nyrop KA, Deal AM, Reeder-Hayes KE, Shachar SS, Reeve BB, Basch E, Choi SK, Lee JT, Wood WA, Anders CK, Carey LA, Dees EC, Jolly TA, Kimmick GG, Karuturi MS, Reinbolt RE, Speca JC, Muss HB (2019) Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: current clinical practice. Cancer 125(17):2945–2954

    CAS  Article  Google Scholar 

  20. 20.

    Jensen MB, Ejlertsen B, Mouridsen HT, Christiansen P (2016) Improvements in breast cancer survival between 1995 and 2012 in Denmark: the importance of earlier diagnosis and adjuvant treatment. Acta Oncol 55(Suppl 2):24–35

    CAS  Article  Google Scholar 

  21. 21.

    Sodergren SC, Copson E, White A, Efficace F, Sprangers M, Fitzsimmons D, Bottomley A, Johnson CD (2016) Systematic review of the side effects associated with anti-HER2-targeted therapies used in the treatment of breast cancer, on behalf of the EORTC quality of life group. Target Oncol 11(3):277–292

    Article  Google Scholar 

  22. 22.

    Gasparini G, Gion M, Mariani L, Papaldo P, Crivellari D, Filippelli G et al (2007) Randomized phase II trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer. Breast Cancer Res Treat 101(3):355–365

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jeanette Dupont Jensen.

Ethics declarations

All patients received oral as well as written information about the project and signed a permission to abstract their electronic patient record. The project was approved by the Danish Data Protection Agency, but approval from the Scientific Ethical Committee for the Region of South Denmark was not needed.

Additional information

Key message

While there are no pharmacological agents known to prevent chemotherapy-induced peripheral neuropathy (CIPN), this study demonstrates that cryotherapy with frozen gloves and socks has the potential to reduce the risk of a dose-limiting event due to CIPN among breast cancer patients receiving weekly paclitaxel in the adjuvant or neo-adjuvant setting. By using cryotherapy from the first cycle of paclitaxel, more patients can complete the planned dose intensity. However, CIPN still remains to be an important dose-limiting toxicity of paclitaxel.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rosenbaek, F., Holm, H.S., Hjelmborg, J.v.B. et al. Effect of cryotherapy on dose of adjuvant paclitaxel in early-stage breast cancer. Support Care Cancer 28, 3763–3769 (2020). https://doi.org/10.1007/s00520-019-05196-z

Download citation

Keywords

  • Breast cancer
  • Cryotherapy
  • Paclitaxel
  • Neuropathy