Presentation, impact and prevention of chemotherapy-induced hair loss: scalp cooling potentials and limitations

Breed, W.P.M.; Hurk, Corina J. van den; Peerbooms, Mijke

doi:10.1586/edm.10.76

Cited by 65 publications

(77 citation statements)

References 88 publications

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“…We also show for the first time that both the active metabolite of cyclophosphamide (4-hydroxy-cyclophosphamide, 4-OH-CP) and docetaxel induce dose-dependent cytotoxicity in NHEKs, an effect which is consistent with the association of these drugs with CIA clinically. The dose-dependence of this toxicity is also in agreement with a number of clinical reports that slower infusion speeds which will lead to a reduced C max cause less severe CIA (Breed et al, 2011). More importantly, our findings that cooling can rescue from cytotoxicity are in concordance with clinical observations that scalp cooling significantly reduces the incidence of CIA following treatment with these drugs (van den Hurk et al, 2012).…”

Section: Discussionsupporting

confidence: 92%

“…Clinically it has been shown that scalp cooling can substantially reduce the incidence of hair loss in response to individual drugs, including cyclophosphamide, doxorubicin and cisplatin (Grevelman and Breed, 2005). However, for combined treatment regimens, and in particular treatment with docetaxel, doxorubicin and cyclophosphamide (clinically known as Taxotere, Adriamycin and Endoxan, or TAC), scalp cooling shows little reported efficacy (Breed et al, 2011;van den Hurk et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…This regimen is being increasingly used in early stage breast cancer but almost always results in CIA and it has been reported that head cooling has very limited success in preventing TAC-mediated CIA, with approximately 90% of patients exhibiting CIA despite using scalp cooling (Breed et al, 2011). Treatment of cells in vitro to mimic clinical administration of TAC posed challenges.…”

Section: Discussionmentioning

confidence: 99%

“…Scalp cooling or hypothermia during the administration of chemotherapy drugs can substantially reduce hair loss (Protiere et al, 2002) and has been used since the 1970s (Dean et al, 1979). Clinically it has been shown that scalp cooling can substantially reduce the incidence of hair loss in response to individual drugs, including cyclophosphamide, doxorubicin and cisplatin (Breed et al, 2011;van den Hurk et al, 2012). However, for combined treatment regimens, such as sequential treatment with docetaxel (taxotere), doxorubicin (adriamycin) and cyclophosphamide (clinically also known as TAC), scalp cooling has limited reported efficacy (Grevelman and Breed, 2005).…”

Section: Abbreviationsmentioning

confidence: 99%

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Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

Al-Tameemi

Dunnill

Hussain

et al. 2014

Toxicology in Vitro

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A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highlycytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection. Chemotherapy-induced alopecia (CIA) is the most common and distressing side effect of anticancer chemotherapy (Wang et al., 2006) and the anxiety caused by the prospect of CIA can cause patients to even refuse treatment in certain cases (Munstedt et al., 1997). Thus development of an effective CIA preventative regime represents an important challenge in oncology (Paus et al., 2013). CIA occurs due to damage to the hair follicles, which comprise various cell types including hair matrix keratinocytes, which represent the most rapidly dividing cell subset and contribute to follicular structure and function (Roh et al., 2005). As chemotherapeutic drugs such as taxanes (e.g. docetaxel), alkylating agents (e.g. cyclophosphamide) and anthracyclines/DNA intercalating agents (e.g. doxorubicin) target cancer cells due to their rapid division rate, these drugs also target the matrix keratinocytes which results in hair loss (Paus et al., 2013). AbbreviationsCurrently the only available preventative treatment for CIA is head (scalp) cooling. Scalp cooling or hypothermia during the administration of chemotherapy drugs can substantially reduce hair loss (Protiere et al., 2002) and has been used since the 1970s (Dean et al., 1979). Clinically it has been shown that scalp cooling can substantially reduce the incidence of hair loss in response to individual drugs, including cyclophosphamide, doxorubicin and cisplatin (Breed et al., 2011;van den Hurk et al., 2012). However, for combined treatment regimens, such as sequential treatment with docetaxel (taxotere), doxorubicin (adriamycin) an...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Abbreviationsmentioning

confidence: 99%

See 2 more Smart Citations

Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

Al-Tameemi

Dunnill

Hussain

et al. 2014

Toxicology in Vitro

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“…The scalp cooling does not provide protection against certain chemotherapeutic classes like taxanes (Christodoulou et al, 2002;Van den Hurk et al, 2013). The common adverse effects associa-ted with the cooling cap system include headaches (induced by cold), shoulder and neck discomfort, and pain because of wearing the cooling cap for a longer time period (Breed et al, 2011). These adverse effects mainly affect the patient compliance.…”

Section: Introductionmentioning

confidence: 99%

Protective role of Nigella sativa in chemotherapy-induced alopecia

Saleem

Sabir

Ahmad

2017

Bangladesh J Pharmacol

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Chemotherapy-induced alopecia affects the pathological as well as the psychological aspects of the cancer patient. In the present study, the protective role of Nigella sativa was evaluated in both adult and newborn albino rats. The anagen phase was first induced. N. sativa oil, N. sativa decoction (5%, 10% and 15%) and minoxidil lotion (standard) were applied daily to the rats two days after the depilation. During the anagen VI phase of the hair follicles, alopecia was induced by giving cyclophosphamide 125 mg/kg, ip to the adult rat and 50 mg/kg to the newborn rats. Cyclophosphamide-induced the alopecia to the whole depilated area of skin in adult rat while alopecia totalis was observed in the newborn rat disease control group. N. sativa oil, N. sativa decoction (5%) showed a significant protective effect against cyclophosphamide-induced alopecia. In conclusion, it is evident that N. sativa provides significant protection against chemotherapy-induced alopecia.Video Clip of Methodology:1 min 43 sec: <a href="https://www.youtube.com/v/AKhk27V3juE">Full Screen</a> <a href="https://www.youtube.com/watch?v=AKhk27V3juE">Alternate</a>

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Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer

Nangia

Wang

Osborne

et al. 2017

JAMA

184

165

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IMPORTANCE Chemotherapy may induce alopecia. Although scalp cooling devices have been used to prevent this alopecia, efficacy has not been assessed in a randomized clinical trial.OBJECTIVES To assess whether a scalp cooling device is effective at reducing chemotherapy-induced alopecia and to assess adverse treatment effects. DESIGN, SETTING, AND PARTICIPANTSMulticenter randomized clinical trial of women with breast cancer undergoing chemotherapy. Patients were enrolled from December 9, 2013, to September 30, 2016. One interim analysis was planned to allow the study to stop early for efficacy. Data reported are from the interim analysis. This study was conducted at 7 sites in the United States, and 182 women with breast cancer requiring chemotherapy were enrolled and randomized.INTERVENTIONS Participants were randomized to scalp cooling (n = 119) or control (n = 63). Scalp cooling was done using a scalp cooling device. MAIN OUTCOMES AND MEASURESThe primary efficacy end points were successful hair preservation assessed using the Common Terminology Criteria for Adverse Events version 4.0 scale (grade 0 [no hair loss] or grade 1 [<50% hair loss not requiring a wig] were considered to have hair preservation) at the end of 4 cycles of chemotherapy by a clinician unaware of treatment assignment, and device safety. Secondary end points included wig use and scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Hospital Anxiety and Depression Scale, and a summary scale of the Body Image Scale.RESULTS At the time of the interim analysis, 142 participants were evaluable. The mean (SD) age of the patients was 52.6 (10.1) years; 36% (n = 51) received anthracycline-based chemotherapy and 64% (n = 91) received taxane-based chemotherapy. Successful hair preservation was found in 48 of 95 women with cooling (50.5%; 95% CI, 40.7%-60.4%) compared with 0 of 47 women in the control group (0%; 95% CI, 0%-7.6%) (success rate difference, 50.5%; 95% CI, 40.5%-60.6%). Because the 1-tailed P value from the Fisher exact test was <.001, which crossed the superiority boundary (P = .0061), the data and safety monitoring board recommended study termination on September 26, 2016. There were no statistically significant differences in changes in any of the scales of quality of life from baseline to chemotherapy cycle 4 among the scalp cooling and control groups. Only adverse events related to device use were collected; 54 adverse events were reported in the cooling group, all grades 1 and 2. There were no serious adverse device events.CONCLUSIONS AND RELEVANCE Among women with stage I to II breast cancer receiving chemotherapy with a taxane, anthracycline, or both, those who underwent scalp cooling were significantly more likely to have less than 50% hair loss after the fourth chemotherapy cycle compared with those who received no scalp cooling. Further research is needed to assess longer-term efficacy and adverse effects.

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Presentation, impact and prevention of chemotherapy-induced hair loss: scalp cooling potentials and limitations

Cited by 65 publications

References 88 publications

Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

Protective role of Nigella sativa in chemotherapy-induced alopecia

Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer

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