Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling

M Martín, J C de la Torre-Montero, S López-Tarruella, K Pinilla, A Casado, S Fernandez, Y Jerez, J Puente, I Palomero, R González Del Val, M Del Monte-Millan, T Massarrah, C Vila, B García-Paredes, J A García-Sáenz, A Lluch, M Martín, J C de la Torre-Montero, S López-Tarruella, K Pinilla, A Casado, S Fernandez, Y Jerez, J Puente, I Palomero, R González Del Val, M Del Monte-Millan, T Massarrah, C Vila, B García-Paredes, J A García-Sáenz, A Lluch

Abstract

Background: Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast cancer (BC) and to test the ability of scalp cooling in prevention.

Patients and methods: BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed.

Results: In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m2 presented a significantly higher prevalence of grades 1 PA (33-52%) and 2 PA (5-12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m2 was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36-13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m2, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m2) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse.

Conclusion: Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m2) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.

Keywords: Alopecia; Breast cancer; Docetaxel; Scalp cooling.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The authors declare that the experiments comply with the current laws of the country in which it was performed.

Figures

Fig. 1
Fig. 1
Persistent alopecia (PA) in patients treated with chemotherapy or endocrine therapy in one of the institutions (HCSC). TAM: tamoxifen; AI: aromatase inhibitors (no chemotherapy); FAC/FEC: 5-fluorouracil,doxorubicin or epirubicin, cyclophosphamide × 6 cycles; ANT-PACL: anthracyclines × 4 cycles followed by paclitaxel; ET-CAP: epirubicin plus docetaxel 75 mg/m2 × 4 cycles, followed by capecitabine; TAC: docetaxel 75 mg/m2, doxorubicin, cyclophosphamide × 6 cycles; ANT-DOCE: anthracyclines × 4 cycles followed by docetaxel 100 mg/m2 × 4 cycles; Around two-thirds of the patients treated with adjuvant chemotherapy received endocrine therapy with tamoxifen, aromatase inhibitors, or both afterwards
Fig. 2
Fig. 2
Persistent alopecina after 46 to 120 months following the conclusion of docetaxel chemotherapy. Panels ai: Grade 2 Persistent Alopecia. Panels jl: Grade 1 Persistent Alopecia (with permission from the patients)

References

    1. Coates A, Abraham S, Kaye SB, et al. On the receiving end-patient perception of the side-effects of cancer chemotherapy. Eur J Cancer Clin Oncol. 1983;19:203–208. doi: 10.1016/0277-5379(83)90418-2.
    1. Hood AF. Cutaneous side effects of cancer chemotherapy. Med Clin N Am. 1986;70:187–209. doi: 10.1016/S0025-7125(16)30976-2.
    1. Katsimbri P, Bamias A, Pavlidis N. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer. 2000;36:766–771. doi: 10.1016/S0959-8049(00)00012-5.
    1. Baker BM, Wilson CL, Davis AL, et al. Busulfan/cyclophosphamide conditioning for bone marrow transplantation may lead to failure to hair re-growth. Bone Marrow Transpl. 1991;7:43–47.
    1. Tosti A, Piraccini BM, Vicenzi C, et al. Permanent alopecia after busulfan chemotherapy. Br J Dermatol. 2005;152:1056–1058. doi: 10.1111/j.1365-2133.2005.06469.x.
    1. Henderson C, Berry D, Demetri G, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–983. doi: 10.1200/JCO.2003.02.063.
    1. Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352:2302–2313. doi: 10.1056/NEJMoa043681.
    1. Childress J, Lokich J. Cutaneous hand and foot toxicity associated with cancer chemotherapy. Am J Clin Oncol. 2003;26:435–436. doi: 10.1097/01.coc.0000026486.56886.18.
    1. Minisini AM, Tosti A, Sobrero AF, et al. Taxane-induced nail changes: incidence, clinical presentation and outcome. Ann Oncol. 2003;14:333–337. doi: 10.1093/annonc/mdg050.
    1. Calhoun EA, Welshman E, Brown S. Taxane-induced alopecia: a historical review of patients with ovarian or breast cancer treated with paclitaxel, docetaxel or paclitaxel poliglumex. J Clin Oncol. 2005;23(1 suppl):740.
    1. Nabholtz JM, Mackey JR, Smylie M. Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. J Clin Oncol. 2001;19:314–321. doi: 10.1200/JCO.2001.19.2.314.
    1. Sedlacek SM. Persistent significant alopecia (PSA) from adjuvant docetaxel after doxorubicin/cyclophosphamide (AC) chemotherapy in women with breast cancer. Breast Cancer Res Treat. 2006;100(suppl1):s116.
    1. Roberts WE. Dermatologic problems of older women. Dermatol Clin. 2006;24:271–280. doi: 10.1016/j.det.2006.01.012.
    1. Rossi A, Iorio A, Scali E, et al. Aromatase inhibitors induce “male pattern hair loss” in women? Ann Oncol. 2013;24:1710–1711. doi: 10.1093/annonc/mdt170.
    1. Kluger N, Jacot W, Frouin E. Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel: a prospective study of 20 patients. Ann Oncol. 2012;23:2879–2884. doi: 10.1093/annonc/mds095.
    1. Fonia A, Cota C, Setterfield F, Goldberg LJ, Fenton DA, Stefanato CM. Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: clinicopathologic findings in a cohort of 10 patients. J Am Acad Dermatol. 2017;76:948–957. doi: 10.1016/j.jaad.2016.12.027.
    1. Rugo HS, Klein P, Melin SA, et al. Association between use of a scalp cooling device and alopecia after chemotherapy for breast cancer. JAMA. 2017;317:606–614. doi: 10.1001/jama.2016.21038.
    1. Nangia J, Wang T, Osborne C, et al. Effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer. The SCALP randomized clinical trial. JAMA. 2017;317:596–605. doi: 10.1001/jama.2016.20939.
    1. Scotté F, Tourani JM, Banu E, et al. Multicenter study of a frozen glove to prevent docetaxel-induced onycholysis and cutaneous toxicity of the hand. J Clin Oncol. 2005;23:4424–4429. doi: 10.1200/JCO.2005.15.651.
    1. Lemieux J, Desbiens C, Hogue JC. Breast cancer scalp metastasis as first metastatic site after scalp cooling: two cases of occurrence after 7- and 9-year follow-up. Breast Cancer Res Treat. 2011;128(2):563–566. doi: 10.1007/s10549-011-1453-y.
    1. Rugo HS, Mellin SA, Voigt J. Scalp cooling with adjuvant/neoadjuvant chemotherapy for breast cancer and risk of scalp metastases: systematic review and meta-analysis. Breast Cancer Res Treat. 2017;163:199–205. doi: 10.1007/s10549-017-4185-9.

Source: PubMed

3
Subscribe