LCD L39573: Scalp Cooling for the Prevention of Chemotherapy-Induced Alopecia

The use of a scalp hypothermia device that has been approved by the United States (U.S.) Food and Drug Administration (FDA) for the prevention of chemotherapy-induced alopecia (CIA) shall be considered reasonable and necessary for patients with solid tumors.

The device is contraindicated for pediatric patients, patients with certain cancers and patients undergoing specific chemotherapy treatments. Usage of the device is contraindicated in:

• Central nervous system malignancies (either primary or metastatic)

• Squamous cell carcinoma and small cell carcinoma of the lung

• Skin cancers including melanoma, squamous cell carcinoma, and Merkel cell carcinoma

• Patients who are scheduled for bone marrow ablation chemotherapy

• Patients who are scheduled to undergo skull irradiation or have previously received skull irradiation

• Patients with a history of scalp metastases, or in whom scalp metastases are suspected

• Patients with cold sensitivity, cold agglutinin disease, cryoglobulinemia, cryofibrinogenemia, and post-traumatic cold dystrophy

• Patients with severe liver or renal disease from any etiology who may not be able to metabolize or clear the metabolites of the chemotherapeutic agent

• Patients with hematologic malignancies (leukemia, non-Hodgkin and other generalized lymphomas)

CIA is a common and well-known side effect of chemotherapy, affecting approximately 65% of patients who undergo chemotherapy for cancer. Total scalp alopecia is most common, but alopecia can also be diffuse or patchy. CIA is most prominent on the scalp, with a predilection for areas with low total hair density, in particular the crown and frontal areas of the scalp, where there is slower hair recovery. CIA is attributed to the cytotoxic effects of chemotherapy drugs on the matrix cells of the hair follicles during hair growth phases. 1,2 Alopecia is usually, although not always, reversible but can be psychologically and socially devastating. CIA has been cited as the most disturbing anticipated side effect by up to 58% of women preparing for chemotherapy, with 8% being at risk for avoiding treatment altogether due to those fears. CIA has been associated with reduced quality of life (QOL), depression, and poor body image, which may endure for months after chemotherapy is completed. 3 A prospective, multi-center study was performed in 13 hospitals to look at the effects of CIA on QOL and associated distress. 4 Breast cancer patients treated with (N=98) and without (N=168) scalp cooling completed questionnaires before chemotherapy, and 3 weeks and 6 months after the last chemotherapy cycle. Scalp cooling was effective in 52% of the cases. Alopecia was considered among the most distressing problems at all 3 moments of measurement. A trend towards higher well-being was found in successfully scalp-cooled patients, as indicated by a general better health-related QOL and better body image, whereas unsuccessfully scalp-cooled patients reported lowest well-being. Recovery generally requires a period of several months to a year, worsening the impact of the disease.

The timing of alopecia depends on the type(s) of systemic therapy agent, dose, and schedule. 5 For most regimens that are given every 2 to 3 weeks, alopecia starts around 2 to 3 weeks, and hair is completely lost by the end of the second cycle of chemotherapy. High-dose, intermittent, intravenous (IV) chemotherapy regimens are associated with a high incidence of ≥ grade 2 alopecia. Weekly chemotherapy generally results in slower and occasionally incomplete alopecia, and hair may start to grow back during treatment. Of the commonly used IV single cytotoxic agents, those most likely to cause complete alopecia (dose and schedule dependent) include alkylating agents (cyclophosphamide, ifosfamide, busulfan, thiotepa), antitumor antibiotics (dactinomycin, doxorubicin, epirubicin, idarubicin), antimicrotubule agents (paclitaxel, docetaxel, ixabepilone, eribulin), and topoisomerase inhibitors (etoposide, irinotecan). 6 Alopecia is less common or incomplete with bleomycin, low-dose epirubicin or doxorubicin (especially 2 ), oral cyclophosphamide, fluorouracil, gemcitabine, melphalan, methotrexate, mitomycin, mitoxantrone, platinum agents (oxaliplatin, cisplatin, and carboplatin), topotecan, and vinca alkaloids. Antibody-drug conjugates are also associated with variable hair loss (HL), which is agent specific. In addition, diffuse or partial alopecia may occur with a number of targeted agents. A new class of targeted agents, termed cyclin-dependent kinase (CDK) 4/6 inhibitors, has demonstrated marked efficacy in combination with endocrine therapy in patients with metastatic hormone receptor-positive breast cancer. Three agents have FDA-approval: palbociclib, ribociclib, and abemaciclib. Given in combination with aromatase inhibitors, these agents increase all-grade and grade 2 alopecia compared with that observed with endocrine therapy alone. There is approximately a doubling of all-grade alopecia, from 10-16% to 25-33%, and approximately a 1.5% increased incidence of grade 2 alopecia. 7

Hair regrowth generally begins by 6 months after the last chemotherapy session; however, HL may be permanent in some patients. 8 , 9 Regrowth to a normal appearance can take up to 1 year. The new hair frequently has different characteristics from the original; 65% of patients experience a graying, curling, or straightening effect, which is likely due to differential effects of chemotherapy on hair follicle melanocytes and inner root sheath epithelia, and these effects often resolve over time. Once CIA occurs, treatment to regrow scalp hair may include topical minoxidil. Minoxidil prolongs the anagen phase and may increase hair follicle size counteracting miniaturization of follicle by androgenic alopecia. Two randomized trials suggest that the effects of topical minoxidil in preventing or treating CIA are limited, at best. In a randomized trial of 48 patients with varying solid tumors receiving doxorubicin-containing regimens, topical minoxidil (2% solution applied twice daily) did not prevent the development of severe alopecia compared with placebo. 10 A second trial in 22 women receiving chemotherapy after surgery for breast cancer also found that treatment with topical minoxidil did not prevent alopecia, but it did shorten the time to maximal regrowth and the time from maximal alopecia to first regrowth, and lengthened the time to maximal alopecia. 11

Although permanent alopecia is uncommon after standard-dose chemotherapy, there is now convincing evidence of permanent or prolonged alopecia after standard-dose chemotherapy for breast cancer (particularly with docetaxel and clearly related to both dose per infusion and duration of exposure). 8