Official reprint from UpToDate® www.uptodate.com
©2012 UpToDate®
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2012 UpToDate, Inc.
Chemotherapy-induced alopecia
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2012. | This topic last updated: Jan 30, 2012.

INTRODUCTION — Hair loss is a transient but often psychologically devastating consequence of cancer chemotherapy. For some patients, the emotional trauma may be so severe as to lead to discontinuing or refusing treatment that might otherwise be beneficial [1-4].

The anatomy and physiology of hair growth, the effects of chemotherapy, and possible means for preventing alopecia are discussed here.

ANATOMY AND PHYSIOLOGY — The hair fiber is the product of the hair follicle and is a complex keratinized structure consisting of a cuticle, cortex and medulla. The hair follicle is composed of three main parts when viewed in longitudinal section (figure 1) [5]:

  • The lower portion, which extends from the base of the hair follicle to the insertion of the arrector pili muscle. This lower portion, in turn, is comprised of several major components:

  • The hair bulb, which contains the dermal papilla and hair matrix. The dermal papilla controls the number of matrix cells, which determines hair size [6]. Melanocytes, which are responsible for hair color, are present among the matrix cells of the hair bulb.
  • The hair itself, consisting of medulla, cortex, and hair cuticle (inside to outside).
  • The inner root sheath, which consists of the inner root sheath cuticle, Huxley layer, and Henle's layer (inside to outside). The inner root sheath is rigid, with its shape determining whether hair is curly or straight.
  • The outer root sheath.

Damage to the lower portion of the hair follicle, as occurs in autoimmune alopecia areata, can result in nonscarring alopecia.

  • The middle portion (isthmus), which extends from the insertion of the arrector pili muscle to the entrance of the sebaceous duct. This portion contains the "bulge" of the hair follicle, where epithelial stem cells reside [7]. Damage to the bulge of the hair follicle results in irreversible scarring alopecia, as is seen clinically in disorders such as discoid lupus and lichen planopilaris.
  • The upper portion (infundibulum), which extends from the entrance of the sebaceous duct to the follicular orifice.

Throughout life, the hair follicle undergoes periods of cyclic growth (anagen, lasting two to six years), regression (catagen, one to two weeks), and dormancy (telogen, three to four months), after which time the hair is shed (also known as exogen) [6,8,9]. Approximately 85 to 90 percent of follicles at any given time are in the active growth phase (anagen). During anagen, mitotically active matrix cells in the hair bulb differentiate and divide, resulting in a rate of hair growth of approximately 0.35 mm per day. Approximately 10 percent of follicles are in telogen (dormancy), during which all mitotic activity is arrested. The remaining 1 to 6 percent are in catagen, the involution phase.

The final step of the hair cycle, exogen, is when the hair is released from the follicle. The scalp is estimated to contain on average 100,000 hairs, of which 100 to 150 are lost daily as part of the normal hair cycle. This loss typically occurs after washing and brushing the hair, so patients who wash their hair less frequently may note a greater number of hairs falling out at each instance.

Multiple signaling molecules have been implicated in the initial development and subsequent cycling of the hair follicle, including Wnt, Sonic Hedgehog, notch, and bone morphogenic proteins, among others [10]. In a mouse model of chemotherapy-induced alopecia, transient overexpression of Sonic hedgehog accelerated hair follicle regrowth [11].

EFFECTS OF CHEMOTHERAPY

Pathophysiology — Cytotoxic chemotherapy attacks rapidly dividing cells in the body, including the dividing hair matrix cells. This can result in hair loss by either of two mechanisms:

  • Thinning of the hair shaft can occur at the time of maximal chemotherapy effect, resulting in Pohl-Pinkus constrictions. As a result, the hair shaft may break at the follicular orifice.
  • If matrix proliferation is severely inhibited, the hair may separate at the bulb and shed, a process referred to as anagen effluvium.

Hair may be completely lost in a short time, as is typically the case for high dose regimens used in the setting of stem cell transplantation, or it may be gradually lost over a period of several weeks, as often occurs with the use of cyclic chemotherapy regimens. Additionally, chemotherapeutic agents such as methotrexate may temporarily affect the follicle melanocytes, resulting in a depigmented band of hair (the so-called "flag sign"). (See "Cutaneous complications of conventional chemotherapy agents", section on 'Hair'.)

The ability of individual agents to cause hair loss depends upon the route, dose, and schedule of drug administration:

  • High-dose, intermittent, intravenous chemotherapy regimens are associated with a high incidence of complete alopecia.
  • Low-dose therapy, oral administration, and weekly regimens are less likely to induce total or complete alopecia [1,2]. As an example, intravenous cyclophosphamide almost universally causes alopecia while oral regimens are less likely to do so.
  • Combination chemotherapy regimens are more likely to result in alopecia than are single agents. Unfortunately, the incidence of alopecia with common regimens has been inconsistently documented in the literature (table 1). (See "Side effects of adjuvant chemotherapy for early stage breast cancer".)

Of the commonly used single cytotoxic agents, those most likely to cause complete alopecia include cyclophosphamide, dactinomycin, bleomycin, doxorubicin, irinotecan, paclitaxel, docetaxel, and topotecan. Hair loss is less common or incomplete with etoposide, fluorouracil, gemcitabine, ifosfamide, melphalan, methotrexate, mitomycin C, mitoxantrone, eribulin, and the vinca alkaloids.

Molecularly-targeted agents — Small molecule inhibitors of the epidermal growth factor receptor (EGFR) as well as monoclonal antibodies targeting the EGFR can induce a constellation of cutaneous symptoms that include an acneiform rash, abnormal hair growth, pruritus, and dry skin; together, this symptom complex is referred to by the acronym PRIDE (Papulopustules and/or paronychia, Regulatory abnormalities of hair growth, Itching, Dryness due to Epidermal growth factor receptor inhibitors). (See "Cutaneous complications of molecularly targeted therapy and other biologic agents used for cancer therapy", section on 'EGFR signal transduction inhibitors'.)

In addition, diffuse alopecia is described as a side effect of these drugs (4 percent with cetuximab). The alopecia is typically non-scarring and therefore reversible. However, at least two reports describe patients on long-term therapy who developed scarring alopecia [12,13]. Interestingly, mice with a targeted deletion in the EGFR gradually develop scarring alopecia [14].

Diffuse, reversible alopecia is also described in up to 50 percent of patients receiving treatment with orally active multitargeted tyrosine kinase inhibitors such as sorafenib and sunitinib [15-18] and in 65 percent of patients treated with vismodegib, an orally active agent approved for advanced basal cell cancer that inhibits sonic hedgehog signaling through competitive antagonist binding of the cell surface receptor smoothened. (See "Cutaneous complications of molecularly targeted therapy and other biologic agents used for cancer therapy", section on 'Small molecule tyrosine kinase signal transduction inhibitors' and "Systemic treatment of advanced cutaneous squamous and basal cell carcinomas", section on 'Vismodegib'.)

Chemotherapy-induced alopecia most commonly affects scalp hair. However, axillary and pubic hair, and even the eyebrows and eyelashes may be lost.

Reversibility — Because chemotherapy effects are typically specific for proliferating cells which reside in the bulb, sparing the quiescent stem cells in the bulge that are responsible for reinitiating follicle growth, hair loss from chemotherapy is usually completely reversible. The hair follicle resumes normal cycling within a few weeks of treatment cessation, and visible regrowth becomes apparent within three to six months. The new hair frequently has different characteristics from the original; 65 percent of patients experience a graying, rejuvenating, curling, or straightening effect, which is likely due to differential effects of chemotherapy on hair follicle melanocytes and inner root sheath epithelia [1].

Permanent alopecia following chemotherapy is rare; most cases have followed the use of high-dose chemotherapy (usually busulfan and cyclophosphamide) and hematopoietic cell transplantation [19-22]. However, there are isolated case reports of permanent alopecia after standard dose chemotherapy for breast cancer (particularly with taxanes) [23,24], and germ cell tumors [20,25]; and long-term use of EGFR inhibitors can also cause permanent alopecia. (See 'Anatomy and physiology' above.)

The impact of hair loss and potential alternative chemotherapy approaches should be discussed with each patient before the initiation of therapy that may lead to alopecia. This preemptive approach is important for minimizing the emotional distress associated with hair loss.

Quantitation of alopecia — A alopecia grading scale for treatment-related alopecia is provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) [26]:

  • Absent (grade 0)
  • Mild (grade 1) – Hair loss of <50 percent of normal for that individual that is not obvious from a distance but only on close inspection; a different hair style may be needed to cover the hair loss but it does not require a wig or hair piece.
  • Severe (grade 2) – Hair loss of ≥50 percent for that individual that is readily apparent to others; a wig or hair piece is necessary if the patient desires to completely camouflage the hair loss; associated with psychosocial impact.

PREVENTION OF ALOPECIA — Therapeutic approaches include physically decreasing the amount of drug delivered to the dividing hair bulb by reducing scalp blood flow and pharmacologic or biologic interventions to block the effects of the chemotherapy.

Decreased drug delivery — There are two physical mechanisms to reduce the amount of chemotherapy reaching the scalp, either with a tourniquet to temporarily obstruct blood flow or by inducing scalp hypothermia that causes vasoconstriction. To be effective, both methods require the use of a chemotherapy agent with a short half-life and rapid clearance of the drug and its metabolites [1,2,4].

Scalp tourniquet — A scalp tourniquet consists of a pneumatic device placed around the hairline during chemotherapy infusion and inflated to a pressure greater than the systolic blood pressure [2]. Several studies have found scalp tourniquets to be effective for preventing hair loss [2,4,27]. However, these studies utilized different techniques with variation in chemotherapy regimens, tourniquet pressure, sample size, and criteria to assess alopecia, rendering the data difficult to interpret. Side effects include headache and varying degrees of nerve compression [2].

Scalp hypothermia — Scalp hypothermia causes vasoconstriction of blood vessels and limits temperature dependent absorption of chemotherapeutic drugs by decreasing the metabolic rate of the hair follicle, thereby inhibiting cellular uptake [1,28-30]. This requires a scalp temperature of less than 24ºC. Side effects include patient discomfort from the heavy caps, cumbersome units, and messiness [1,4,28,31-33].

The drugs best suited to this approach include doxorubicin, daunorubicin, paclitaxel, epirubicin, vincristine, vinblastine, actinomycin D and mechlorethamine. Success with combination regimens such as intravenous cyclophosphamide, methotrexate and fluorouracil (CMF) has been reported, but this approach failed with the combination of doxorubicin plus cyclophosphamide [34-37].

Results of many studies are difficult to interpret secondary to use of multiple cooling systems (ice turban, gel packs, cool caps, thermocirculator, room air conditioner), variable chemotherapy regimens (single versus combined agents), small study populations, and varying definitions of alopecia [1,2,4]. Nevertheless, at least three randomized controlled trials suggest significantly less hair loss with scalp hypothermia [27,34,38,39]. Between 50 and 80 percent of patients have a good to excellent response with this therapy [1,27,34,38,40,41].

Scalp hypothermia may not be as effective in patients with liver dysfunction [1,2,4,28,30,33,38]. This is likely related to delayed drug metabolism, thereby allowing persistence of therapeutic drug levels beyond the protective period.

Some investigators have raised concerns regarding the possibility of scalp metastasis in association with scalp hypothermia [1,2,27-29,33,38,42]. As an example, one group reported the outcome of a patient with mycosis fungoides who used a cooling cap to prevent alopecia [42]. Following chemotherapy, he developed recurrent disease limited to the scalp. Subsequent treatment without a cooling device resulted in complete clinical remission.

However, the clinical significance of these findings is unclear in patients with solid tumors. In one study of 61 patients with disseminated breast cancer receiving chemotherapy who used a cooling cap, one patient with underlying liver dysfunction developed cutaneous scalp metastasis [28]. In contrast, three separate series, either entirely or predominantly consisting of patients receiving adjuvant treatment for breast cancer reported no increased frequency of scalp metastases in the patients who were treated in conjunction with a scalp cooling device [29,41,43].

These case reports suggest that cooling devices may be contraindicated in patients with circulating tumor cells (eg, lymphoma, leukemia) or in those with liver dysfunction resulting in prolonged drug half-lives. They should be used with caution in patients with breast carcinoma, especially in the setting of adjuvant therapy, as well as other carcinomas associated with risk for cutaneous metastases, such as lung, kidney, stomach, colon, and uterus.

Pharmacologic interventions — Preliminary studies have suggested that a variety of both small molecules and biologic agents may reduce or prevent alopecia by protecting the hair bulb from the damaging effects of chemotherapy. Unfortunately, none of these agents have demonstrated adequate activity in large, randomized clinical trials to justify their general usage.

Topical minoxidil — Minoxidil is thought to modify the hair cycle by prolonging the anagen phase. It may also increase hair follicle size, thereby counteracting the miniaturization of the hair follicle that is the characteristic histologic finding of androgenetic alopecia. Minoxidil has been used for treatment of androgenetic alopecia and alopecia areata. Two randomized trials suggest that the effects of minoxidil in preventing or treating chemotherapy-induced alopecia are at best very limited:

  • In a randomized trial of 48 patients with varying solid tumors receiving doxorubicin-containing regimens, topical minoxidil (2 percent solution applied twice daily) did not prevent the development of severe alopecia compared to placebo [44].
  • 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 hair loss to first regrowth and lengthened the time to maximal hair loss [45].

AS101 — AS101 (ammonium trichloro (dioxoethlyene-O,O'-) tellurate) is a synthetic compound that acts as an immunomodulator and has minimal toxicity [46]. It stimulates both mouse and human lymphocytes to proliferate and secrete a variety of cytokines in vitro and in vivo [46,47].

The protective effect of this compound on hair loss was incidentally observed in a study investigating whether AS101 could prevent chemotherapy-induced neutropenia and thrombocytopenia. In 44 patients with advanced non-small cell lung cancer who were randomly assigned to receive carboplatin plus etoposide with or without AS101, the group receiving AS101 had a significantly lower incidence of severe alopecia (17 versus 62 percent) despite receiving more drugs (100 percent of planned doses versus 20 percent for the chemotherapy only group) [48]. The only adverse side effects noted with AS101 were garlic-like halitosis and post-infusional-fevers.

The mechanism by which AS101 prevents alopecia may be related to its ability to stimulate IL-1 production. In rats, IL-1 has been shown to prevent hair loss due to concurrent chemotherapy. In humans, there is a negative correlation between the levels of IL-1 and the degree of alopecia (see 'Interleukin-1' below). In addition, IL-1 receptor antagonists abrogate the protective effects of IL-1 [46-49].

These observations with AS101 have not been confirmed in additional trials, and this agent is not commercially available.

Alpha tocopherol — Alpha tocopherol was initially reported to reduce the incidence of alopecia in a study of patients given high doses of alpha tocopherol (1600 international units daily) for cardioprotection during doxorubicin therapy [50]. Subsequently, two prospective studies were unable to replicate this observation [51,52]. In one trial of 25 female patients with breast cancer, there was no difference in significant alopecia between controls and a study group that received alpha tocopherol (1600 international units daily for seven days prior to therapy) [51]. In the second report, 18 of 20 women with solid tumors receiving various doxorubicin-containing regimens developed significant alopecia despite seven days of pretreatment with high-dose alpha tocopherol [52].

Inhibitors of cyclin-dependent kinase — Inhibitors of cyclin-dependent kinase 2 (CDK2), a regulator of cell cycle progression, may reduce the sensitivity of the hair follicle epithelium to cell-cycle active cytotoxic agents. In one preclinical report, topical application of small molecule inhibitors of CDK2 reduced chemotherapy-related hair loss in rats by 33 to 50 percent [53].

Inhibitors of p53 — Mice deficient for p53 do not develop chemotherapy-induced alopecia [54]. The mechanism for protection is thought to be inhibition of hair follicle apoptosis, due to down-regulation of Fas and increased expression of Bcl-2. This observation suggests that local pharmacologic inhibition of p53 might be useful to prevent chemotherapy-associated hair loss.

Imuvert — Imuvert is a biological response modifier produced by the bacterium Serratia marcescens. It consists of a membrane vesicle-ribosome preparation derived from a series of lytic and centrifugal steps [55,56]. It was initially developed to perform immunomodulating or immunorestorative properties for malignancies where immune system dysfunction had occurred [2].

In animal experimental models, imuvert has been found to induce the cytokines IL-1, TNF, Interferon alpha, IL-6, GM-CSF, and PDGF [55,56]. In rats, imuvert protected against cytarabine- and doxorubicin-induced but not cyclophosphamide-induced alopecia. However, imuvert did protect against cyclophosphamide plus cytarabine (ARA-C) induced alopecia when N-acetylcysteine was added either parentally or topically in liposomal preparation [55]. There are no published human data to date.

Biologic response modifiers — There have been several studies evaluating the efficacy of epidermal growth factor (EGF) and fibroblast growth factor (FGF) in preventing hair loss [57]. Systemically administered EGF protected rats from cytarabine but not cyclophosphamide-induced alopecia, while topical application of EGF prevented alopecia at the site of administration only. Injectable FGF prevented hair loss at the local injection site. The biological mechanism of this action is unclear, as EGF receptor inhibition with cetuximab has been associated with both alopecia and trichomegaly [58].

Topical cyclosporine — Selected immunophilin ligands such as cyclosporine A (CsA) and FK 506 are not only potent immunosuppressants but also modulate hair growth. In murine models, topical application of CsA and FK 506 induced hair growth and inhibited cyclophosphamide-induced hair loss [37]. In another in vivo model, topical CsA protected rat models from site-specific alopecia when coadministered with etoposide, cyclophosphamide, cytarabine, and doxorubicin [59].

The mechanism of this benefit is unknown. Drugs that act at the hair bulb are assumed to protect the hair follicle keratinocytes against the effects of chemotherapy, possibly through the expression of p-glycoprotein. Cyclosporine has been studied topically in rat models and found to inhibit p-glycoprotein and a hypotrichotic agent [59]. Cyclosporine also increases IL-1 receptor expression [60], which may further enhance its ability to prevent alopecia.

Interleukin-1 — Interleukin-1 (IL-1) mediates a variety of activities involved in host defense and disease processes. Mononuclear phagocytes, keratinocytes, glial cells, and endothelial cells are all known to produce IL-1 [2]. Dermal and epidermal cells possess IL-1 receptors and are capable of secreting the cytokines thought to play a role in inflammation in the skin.

Administration of IL-1 protects against the alopecia related to chemotherapy and radiation therapy in animals [61-63]. In one study, 48 rats were randomly assigned into four groups that received either cyclophosphamide or cytarabine, with or without IL-1 [63]. The rats treated with cytarabine, a cell-cycle specific agent, were protected against significant alopecia by the addition of IL-1. However, the rats who received non cell-cycle specific chemotherapeutic agents were not protected. These results led to the hypothesis that cell-cycle specific and cell-cycle nonspecific agents induce alopecia via different mechanisms.

IL-1 appears to function at the level of the hair follicle to protect against alopecia. However, evidence is lacking as to whether IL-1 directly or indirectly stimulates the cytokines involved in hair follicle growth [61,62].

Topical calcitriol — Pretreatment with topical calcitriol (1,25(OH)2D3, the most active metabolite of vitamin D) protects rats from cyclophosphamide-, etoposide-, and doxorubicin-induced alopecia [64]. Effects may be mediated by direct biological activity or modulation of other factors. Specific receptors for calcitriol are present in rat, murine, and human skin cells, and calcitriol induces differentiation of murine epidermal keratinocytes. When human cultured keratinocytes are incubated with calcitriol, there is a dose- and time-dependent stimulation of differentiation and inhibition of DNA synthesis.

One study found that pretreatment with calcitriol did not alter the cytotoxic effects of the chemotherapy but did prevent significant alopecia [65]. However, other data suggest that calcitriol can inhibit growth and/or induce differentiation of some cancer cell lines [64-66]. These concerns regarding the potential for calcitriol to protect cancer cells in addition to hair follicles from the effects of chemotherapy have limited enthusiasm for this approach.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS — Hair loss is a transient but often psychologically devastating consequence of cancer chemotherapy. A wide range of chemotherapy agents can affect the growing cells of the hair follicle. The frequency and severity of alopecia varies depending upon the specific chemotherapy agent or combination regimen administered, the dosage of drugs, and the treatment schedule. The majority of chemotherapy-induced alopecia is reversible once therapy is discontinued, with the possible exception of the epidermal growth factor receptor (EGFR) inhibitors. (See 'Effects of chemotherapy' above.)

  • All patients who will receive chemotherapy that may result in alopecia should be informed of the likely side effect of hair loss. Options such as head wraps, hats, or wigs should be discussed in advance so that the patient can be more physically and emotionally prepared. (See 'Effects of chemotherapy' above.)
  • Although scalp protection through cooling or tourniquet has been reported to minimize delivery of chemotherapeutic agents to the scalp thereby potentially decreasing the risk of hair loss, case reports of cutaneous metastases or spread in these settings prevent general recommendation for their use. Because chemotherapy-associated hair loss is transient and completely reversible after cessation of therapy, adequate counseling and psychological support before and during therapy should take precedence over the use of such devices. (See 'Decreased drug delivery' above.)
  • Currently there are no available pharmacologic interventions that have been shown to decrease the risk of chemotherapy-induced alopecia. Although minoxidil has not shown efficacy in preventing chemotherapy-induced alopecia, the use of minoxidil during the period of regrowth may help to minimize hair follicle miniaturization in patients at risk for androgenetic alopecia. (See 'Pharmacologic interventions' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

  1. Dorr VJ. A practitioner's guide to cancer-related alopecia. Semin Oncol 1998; 25:562.
  2. Hussein AM. Chemotherapy-induced alopecia: new developments. South Med J 1993; 86:489.
  3. Bruning N. Hair, skin, and nail effects. In: Coping with chemotherapy, Dial Press, Garden City, NY 1985. p.191.
  4. Cline BW. Prevention of chemotherapy-induced alopecia: a review of the literature. Cancer Nurs 1984; 7:221.
  5. Elder D, Elenitsas R, Johnson BL, Murphy GF. Lever's Histopathology of the Skin, 9th ed, Lippincott Williams & Wilkins, Philadelphia 2004. p.1229.
  6. Paus R, Cotsarelis G. The biology of hair follicles. N Engl J Med 1999; 341:491.
  7. Liu Y, Lyle S, Yang Z, Cotsarelis G. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. J Invest Dermatol 2003; 121:963.
  8. James WD, Berger T, Elston D. Andrews' Diseases of the Skin. In: Clinical Dermatology, 10th ed, WB Saunders, Philadelphia 2005.
  9. Yang CC, Cotsarelis G. Review of hair follicle dermal cells. J Dermatol Sci 2010; 57:2.
  10. Cotsarelis G, Millar SE. Towards a molecular understanding of hair loss and its treatment. Trends Mol Med 2001; 7:293.
  11. Sato N, Leopold PL, Crystal RG. Effect of adenovirus-mediated expression of Sonic hedgehog gene on hair regrowth in mice with chemotherapy-induced alopecia. J Natl Cancer Inst 2001; 93:1858.
  12. Wu CY, Chen GS, Lan CC. Erosive pustular dermatosis of the scalp after gefitinib and radiotherapy for brain metastases secondary to lung cancer. Clin Exp Dermatol 2008; 33:106.
  13. Donovan JC, Ghazarian DM, Shaw JC. Scarring alopecia associated with use of the epidermal growth factor receptor inhibitor gefitinib. Arch Dermatol 2008; 144:1524.
  14. Murillas R, Larcher F, Conti CJ, et al. Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure. EMBO J 1995; 14:5216.
  15. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356:125.
  16. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359:378.
  17. Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006; 24:2505.
  18. Autier J, Escudier B, Wechsler J, et al. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol 2008; 144:886.
  19. Machado M, Moreb JS, Khan SA. Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40:979.
  20. Palamaras I, Misciali C, Vincenzi C, et al. Permanent chemotherapy-induced alopecia: a review. J Am Acad Dermatol 2011; 64:604.
  21. Ljungman P, Hassan M, Békássy AN, et al. Busulfan concentration in relation to permanent alopecia in recipients of bone marrow transplants. Bone Marrow Transplant 1995; 15:869.
  22. Vowels M, Chan LL, Giri N, et al. Factors affecting hair regrowth after bone marrow transplantation. Bone Marrow Transplant 1993; 12:347.
  23. Tallon B, Blanchard E, Goldberg LJ. Permanent chemotherapy-induced alopecia: case report and review of the literature. J Am Acad Dermatol 2010; 63:333.
  24. Prevezas C, Matard B, Pinquier L, Reygagne P. Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer. Br J Dermatol 2009; 160:883.
  25. de Jonge ME, Mathôt RA, Dalesio O, et al. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy. Bone Marrow Transplant 2002; 30:593.
  26. National Canceer Institute Common Terminology Criteria for Adverse Events 9CTCAE), v4.03 available online at http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.
  27. Satterwhite B, Zimm S. The use of scalp hypothermia in the prevention of doxorubicin-induced hair loss. Cancer 1984; 54:34.
  28. Vendelbo Johansen L. Scalp hypothermia in the prevention of chemotherapy-induced alopecia. Acta Radiol Oncol 1985; 24:113.
  29. Tollenaar RA, Liefers GJ, Repelaer van Driel OJ, van de Velde CJ. Scalp cooling has no place in the prevention of alopecia in adjuvant chemotherapy for breast cancer. Eur J Cancer 1994; 30A:1448.
  30. Symonds RP, McCormick CV, Maxted KJ. Adriamycin alopecia prevented by cold air scalp cooling. Am J Clin Oncol 1986; 9:454.
  31. Tierney A, Taylor J, Closs SJ, et al. Hair loss due to cytotoxic chemotherapy: A prospective descriptive study. Br J Cancer 1990; 62: 527.
  32. Lemenager M, Genouville C, Bessa EH, Bonneterre J. Docetaxel-induced alopecia can be prevented. Lancet 1995; 346:371.
  33. Lemenager M, Lecomte S, Bonneterre ME, et al. Effectiveness of cold cap in the prevention of docetaxel-induced alopecia. Eur J Cancer 1997; 33:297.
  34. Parker R. The effectiveness of scalp hypothermia in preventing cyclophosphamide-induced alopecia. Oncol Nurs Forum 1987; 14:49.
  35. Knobf M, Kalm D, Mealia M. Clinical observations of scalp cooling in patients receiving multidrug chemotherapy. Oncol Nurs Forum 1989; 16(suppl):200.
  36. Middleton J, Franks D, Buchanan RB, et al. Failure of scalp hypothermia to prevent hair loss when cyclophosphamide is added to doxorubicin and vincristine. Cancer Treat Rep 1985; 69:373.
  37. Maurer M, Handjiski B, Paus R. Hair growth modulation by topical immunophilin ligands: induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia. Am J Pathol 1997; 150:1433.
  38. Giaccone G, Di Giulio F, Morandini MP, Calciati A. Scalp hypothermia in the prevention of doxorubicin-induced hair loss. Cancer Nurs 1988; 11:170.
  39. Lotfi-Jam K, Carey M, Jefford M, et al. Nonpharmacologic strategies for managing common chemotherapy adverse effects: a systematic review. J Clin Oncol 2008; 26:5618.
  40. Katsimbri P, Bamias A, Pavlidis N. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer 2000; 36:766.
  41. Spaeth D, Luporsi E, Weber B, et al. Efficacy and safety of cooling helmets (CH) for the prevention of chemotherapy-induced alopecia (CIA): A prospective study of 911 patients (abstract). J Clin Oncol 2008; 26:517s. (Abstract available online at www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=31510, accessed September 8, 2008).
  42. Witman G, Cadman E, Chen M. Misuse of scalp hypothermia. Cancer Treat Rep 1981; 65:507.
  43. Ron IG, Kalmus Y, Kalmus Z, et al. Scalp cooling in the prevention of alopecia in patients receiving depilating chemotherapy. Support Care Cancer 1997; 5:136.
  44. Rodriguez R, Machiavelli M, Leone B, et al. Minoxidil (Mx) as a prophylaxis of doxorubicin--induced alopecia. Ann Oncol 1994; 5:769.
  45. Duvic M, Lemak NA, Valero V, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol 1996; 35:74.
  46. Sredni B, Caspi RR, Klein A, et al. A new immunomodulating compound (AS-101) with potential therapeutic application. Nature 1987; 330:173.
  47. Kalechman Y, Albeck M, Oron M, et al. Protective and restorative role of AS101 in combination with chemotherapy. Cancer Res 1991; 51:1499.
  48. Sredni B, Albeck M, Tichler T, et al. Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide. J Clin Oncol 1995; 13:2342.
  49. Sredni B, Xu RH, Albeck M, et al. The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia studies on human and animal models. Int J Cancer 1996; 65:97.
  50. Wood LA. Possible prevention of adriamycin-induced alopecia by tocopherol. N Engl J Med 1985; 312:1060.
  51. Martin-Jimenez M, Diaz-Rubio E, Gonzalez Larriba JL, Sangro B. Failure of high-dose tocopherol to prevent alopecia induced by doxorubicin. N Engl J Med 1986; 315:894.
  52. Perez JE, Macchiavelli M, Leone BA, et al. High-dose alpha-tocopherol as a preventive of doxorubicin-induced alopecia. Cancer Treat Rep 1986; 70:1213.
  53. Davis ST, Benson BG, Bramson HN, et al. Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science 2001; 291:134.
  54. Botchkarev VA, Komarova EA, Siebenhaar F, et al. p53 is essential for chemotherapy-induced hair loss. Cancer Res 2000; 60:5002.
  55. Jiménez JJ, Huang HS, Yunis AA. Treatment with ImuVert/N-acetylcysteine protects rats from cyclophosphamide/cytarabine-induced alopecia. Cancer Invest 1992; 10:271.
  56. Hussein AM, Jimenez JJ, McCall CA, Yunis AA. Protection from chemotherapy-induced alopecia in a rat model. Science 1990; 249:1564.
  57. Jimenez JJ, Yunis AA. Protection from 1-beta-D-arabinofuranosylcytosine-induced alopecia by epidermal growth factor and fibroblast growth factor in the rat model. Cancer Res 1992; 52:413.
  58. Dueland S, Sauer T, Lund-Johansen F, et al. Epidermal growth factor receptor inhibition induces trichomegaly. Acta Oncol 2003; 42:345.
  59. Hussein AM, Stuart A, Peters WP. Protection against chemotherapy-induced alopecia by cyclosporin A in the newborn rat animal model. Dermatology 1995; 190:192.
  60. Degiannis D, Stein S, Czarnecki M, et al. Cyclosporine-induced enhancement of interleukin 1 receptor expression by PHA-stimulated lymphocytes. Transplantation 1990; 50:1074.
  61. Jimenez JJ, Wong GH, Yunis AA. Interleukin 1 protects from cytosine arabinoside-induced alopecia in the rat model. FASEB J 1991; 5:2456.
  62. Jimenez JJ, Sawaya ME, Yunis AA. Interleukin 1 protects hair follicles from cytarabine (ARA-C)-induced toxicity in vivo and in vitro. FASEB J 1992; 6:911.
  63. Hussein AM. Interleukin 1 protects against 1-beta-D-arabinofuranosylcytosine-induced alopecia in the newborn rat animal model. Cancer Res 1991; 51:3329.
  64. Jimenez JJ, Yunis AA. Protection from chemotherapy-induced alopecia by 1,25-dihydroxyvitamin D3. Cancer Res 1992; 52:5123.
  65. Jimenez JJ, Alvarez E, Bustamante CD, Yunis AA. Pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia without protecting the leukemic cells from Cytoxan. Am J Med Sci 1995; 310:43.
  66. Reichel H, Koeffler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. N Engl J Med 1989; 320:980.
Topic 1156 Version 9.0

All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.