(pre-)Clinical research to understand alopecia and improve cooling results
C. van den Hurk1, M. Komen2, O. Hussain3, 4, W. Al-Tameemi3, R. Paus5, 6, A. Collett3, I. Haslam5, A. Young7, H. Mc Vicars8, J. Ross9, N. T. Georgopoulos3
Author Affiliations
1Netherlands Comprehensive Cancer Organisation, IKNL (NL)
2Medical Centre Alkmaar (NL)
3Huddersfield University (GB)
4Paxman Coolers Ltd (GB)
5Manchester University (GB),
6Münster University (DE)
7Warwick University (GB)
8Western General Hospital (GB)
9Royal Marsden Hospital (GB)
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ViewAbstract
Purpose
• Authors: international multi-disciplinary special interest group (SIG) on chemotherapy-induced alopecia (CIA) & scalp cooling
• Pathobiology of CIA is still not fully understood1
• Prevention of CIA by scalp cooling (Fig 1):
– Well tolerated by patients
– Overall 50% satisfactory results
– Increasingly used world wide
• Goal of SIG: study CIA by combining pre-clinical & clinical research, ultimately improving efficacy of scalp cooling
Methods
Study mechanism of CIA & preventative role of cooling:
A. Studying in vitro cell toxicity models, using a variety of cultured keratinocytes (including human hair follicular keratinocytes, normal epidermal human keratinocytes & immortalised human keratinocytes)
B. Clinical investigation into the role of post-infusion scalp cooling times (PICT) & scalp skin temperature on severity of CIA
C. Investigate intracellular pathways mediating damage to human hair follicle-associated cell populations
Results
A. Cooling rescues cells in culture from cytotoxicity caused by doxorubicin, docetaxel & the active metabolite of cyclophosphamide (4-OH-cyclophosphamide) (Fig 2 & 3).2 Observations are extended to series of other commonly used chemotherapy drugs, e.g. paclitaxel
B. No significant differences in CIA found for PICTs of 90, 45 & 20 minutes in 3-weekly docetaxel chemotherapy (75 or 100 mg/m2).3 Degree of CIA is temperature dependent, best results for anthracyclines obtained at temperatures <20ºC4
C. A feasible method to determine P53 in hair follicle-associated cell populations has been developed
Conclusion
• Cooling reduces cell death when exposed to a range of chemotherapeutic drugs, reflecting clinical outcomes
• Dose is a determining factor, but half-life times of cytotoxics do not seem to be the most important factor for the optimal PICT
• Adapting scalp cooling temperatures to individual scalp skin temperatures could enhance results
• Combining pre-clinical & clinical research supports development of a patient tailored approach with the ultimate goal to prevent CIA for our patients & thereby improve their quality of life
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