04 Nov Scalp Cooling Prevents Chemotherapy Induced Hair Loss
Medical Research: What is the background for this study? What are the main findings?
Dr. Georgopoulos: Chemotherapy-induced alopecia (CIA) is one of the most distressing side effect of chemotherapy and the anxiety caused by the prospect of Chemotherapy-induced alopecia can cause some cancer patients to even refuse treatment. Various classes of chemotherapeutic drugs such as taxanes (e.g. docetaxel), alkylating agents (e.g. cyclophosphamide) and anthracyclines/DNA intercalating agents (e.g. doxorubicin) target tumour cells due to their rapid division rate; however, these drugs also target the hair matrix keratinocytes, the most rapidly dividing cell subset in the hair follicle, thus resulting in follicle damage and ultimately hair loss.
The only currently available preventative treatment for Chemotherapy-induced alopecia is head (scalp) cooling; scalp cooling during chemotherapy drug administration can substantially reduce hair loss and has been used since the 1970s. However, until recently there was inadequate biological data to support the cyto-protective capacity of cooling; yet such experimental evidence would be important to convince clinicians and patients of the efficacy of cooling. Moreover, it is not clear why in some patients scalp cooling fully protects from Chemotherapy-induced alopecia whereas in other patients it is less efficient. Finally, although scalp cooling can substantially reduce the incidence of hair loss in response to individual drugs, for some combined treatment regimens scalp cooling has much lower (and often quite limited) reported efficacy. Collectively, the need to answer these questions, and to provide ‘real’ experimental data that will support the ability of cooling to ‘rescue’ cells from the cytotoxic effects of chemotherapy drugs, led us to carry out the study.
Using several cell culture models (including human hair follicular keratinocytes), we showed for the first time that cooling dramatically reduces or completely prevents the cytotoxic capacity of drugs such as docetaxel, doxorubicin and the active metabolite of cyclophosphamide (4-OH-CP), whilst combinatorial treatment showed relatively poor response to cooling. Our experimental, in vitro findings are in close agreement with clinical observations. Moreover, we have provided evidence that the minimum temperature achieved may be critical in determining the efficacy of cooling; as the lowest temperature achieved by scalp cooling can differ between patients (our unpublished observations), our findings may also explain why cooling protects from Chemotherapy-induced alopecia better in some patients but not others.
Medical Research: What should clinicians and patients take away from your report?
Dr. Georgopoulos: By showing that hair follicle cells, which are those targeted and killed by chemotherapy drugs, can be extremely well protected from the toxicity of these drugs under cooling conditions, our study has provided for the first time experimental evidence supporting the cytoprotective capacity of cooling. We believe that on the basis of this biological evidence both clinicians and patients will now be convinced of the protective ability of cooling. We hope that more clinicians will be recommending scalp cooling to cancer patients undergoing chemotherapy and in the near future scalp cooling will become standard practice in the clinic worldwide. In addition, the patients, by being aware of the efficacy of cooling, will be more encouraged to request the use of the cooling cap during chemotherapy treatment that will reduce the anxiety and trauma caused by hair loss.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Georgopoulos: The concordance of our laboratory observations with the clinical findings obtained in patients undergoing scalp cooling during chemotherapy indicates that, despite their reductive nature, these robust and reproducible in vitro models may improve our understanding of Chemotherapy-induced alopecia and permit detailed investigations into the mechanisms that underpin cell cooling-mediated cytoprotection to chemotherapeutic drugs.
We are currently investigating the molecular mechanisms driving cytotoxicity by these drugs and already have generated some interesting observations with regards to the ability of cooling to alter these intracellular responses. We believe that by understanding these mechanisms, we will be able to determine why cooling protects against some chemotherapy modalities but not others. This may allow us to design better cooling-based strategies either by modifying the duration of the cooling period and the scalp temperature itself, or even by combining scalp cooling with pharmacological agents that target relevant intracellular cytotoxicity mediators to enhance cytoprotection.
Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity
Al-Tameemi W, Dunnill C, Hussain O, Komen MM, van den Hurk CJ, Collett A, Georgopoulos NT
Toxicol In Vitro. 2014 Dec;28(8):1366-76. doi: 10.1016/j.tiv.2014.07.011.
Epub 2014 Aug 1.