Professor Robert Thomas. Consultant Oncologist, Addenbrooke’s and Bedford Cambridge University Hospitals. Professor of Biological and Exercise Science Coventry University.
Introduction:
There is increasing awareness of benefits of dietary phytochemicals particularly polyphenols [Thomas. These gifts from nature enhance the look, smell and taste of food and have complex bioactive properties which have been shown to reduce the risk of cancer [Buck, help prevent it progressing [Thomas and reduce the risk of relapse [Zhu. Higher intakes of polyphenols have also been linked to better recovery after exercise [Thomas, lower the risk of diabetes [Du, arthritis [Shen and other chronic inflammatory diseases [Thomas.
‘Their potential benefits as topical treatments have been largely overlooked, by the scientific community, until this major UK randomized double blind was conducted and presented at this year’s prestigious American Society of Clinical Oncology conference in Chicago. It evaluated a nail bed balm that harnessed the natural properties of polyphenol rich African oils and waxes and reported a profound reduction of chemotherapy induced nail damage and a major improvement in nail related quality of life.
Background to the study:
Nails are made by living stem cells and, because they are dividing rapidly, are especially susceptible to chemotherapy [Wasner. As a consequence, disfiguring nail damage is common, especially following regimens containing taxanes used for men and women with breast and prostate cancer [Minisini. The type and severity of damage is variable, but most intravenous regimens can cause ridges in nails, which correspond to the timings of chemotherapy episodes known as ‘Beau’s lines’. More pronounced chemotherapy nail damage leads to discolouration, brittle nails, acute paronychia, onycholysis and sometimes even complete loss of the nail. This damage is often unsightly and contributes to body image issues during chemotherapy [Ding. More serious consequences include pain, which can limit activities of daily living, and secondary infection. This is of particular concern when patients are also neutropenic as the nails could be a source of systemic infection.
How does chemotherapy damage the nails:
In addition to the killing of rapidly proliferating nail stem cells, damage is also thought to be due to chemotherapy’s anti-angiogenetic and neurogenically mediated inflammatory properties [Batergay. In addition, if the damage is marked, the nails can separate from the bed causing pain, secondary bacterial and fungal infections considerably further increasing damage to the nail [Minisini, wasner, Ding
Existing advice:
A variety of anecdotal strategies are advised to patients during chemotherapy including nail hygiene, wearing nail varnish and avoiding trauma. We have previously published a report showing that cooling the nails bed with pots of iced water helps to reduce its severity [Ding. Understandably, the practice has never caught on within the confines of a busy chemotherapy unit. Commercially available cooling gloves are available but they are not particularly popular among UK chemotherapy nurses as they may cover the veins of the hands and prevent assessment of the patient’s extremities [Scottie, Ishiguro.
Many patient advocacy groups advise massaging moisturising balms into the nail bed, based on assumptions that oiling skin around the cuticles could improve compliance, thus preventing splitting which can be a route for infection and damage the nail bed. Although this seems intuitively beneficial there are no studies to support this practice or advise which balms to use. Patients are also often advised to wear nail varnish despite the knowledge that nail polish removers dry the nails. Likewise, there are no published prospective trials to support this practice during chemotherapy, or in an otherwise healthy population.
With this lack of evidence in mind, a scientific committee was formed for this study with the aim of reviewing the existing laboratory and clinic data, develop a workable potential solution and designing a major randomised trial to investigate its effectiveness. The committee consisted of experienced oncologist, nurses and patients themselves from Bedford, Cambridge, Bristol and London. They collaborated closely with the National Lifestyle and Behavioural change work stream of the Department of Health backed National Cancer Research Network, advisors from the Department of Biological science at Coventry University and independent statisticians to ensure the best possible, robust and authenticated design.
The hypothesis for this plant based balm:
The scientific rationale for the bases, waxes and essential oils, chosen for this study, are described in detail on the trials website (cancernet.co.uk/polybalm.htm). They are particularly rich in phytochemical especially the phenolic polyphenols group. In addition to they basic abilities to mosturizing the skin and prevent drying, splitting or cracking of the nail, they are known to have anti-inflammatory and anti-oxidant properties [Delaquis, Smith-Palmer, Baratta. It was hypothesized that oils with these properties, applied locally to the nail bed, would be sufficient absorption to act as a local antidote to the chemotherapy, preventing damage to the proliferating stem cells. In addition their anti-microbial properties would help prevent secondary infection so overall keeping the nail healthy and intact [Delaquis, Smith-Palmer, Baratta.
The study design
Sixty men and women receiving chemotherapy for breast or prostate cancer were randomised to apply either a simple petroleum based moisturising balm to their nail beds three times a day or the investigational balm. Both groups were given general advice on how to protect their nails during chemotherapy (see keep-healthy.com). An information video is now available on how best to apply the nail balm on both the nails of the hand and the feet (see polybalm.com). Neither balm contained any potential irritants such as preservatives, parabens, sulphates or petroleum. The controlled contained petroleum and fragrances and the plant based balm contained cold pressed extra virgin olea europaea, unrefined shea butter (butyrospermun parkii), theobroma cacao, organic beeswax (cera alba) African salvia officinalis (leleshwa), gaultheria procumbens, lavandula officinalis, eucalyptus globulus, tarchonanthus camphoratus.
Trial measurements and outcomes:
The health of the nails were measured by 4 independent tools and none of the patients, doctors, research team or statistician knew which balm was assigned to which participant.
Patients
recorded their own nail health with the validated Dermatology Life Quality questionnaire (DLQQ) plus a simple linear severity scale (LSS) that emphasised how the nail damage affected their daily activities and quality of life.
Physicians
recorded the physical condition of the nails using the validated Nail Psoriasis Index (NPSI) plus another simple linear severity scale (LSS). As well as directly scoring nail damage, photographs of the nails were sent to 3 doctors from other departments and hospitals for further independent verification.
In all but 2 of the 30 patients in the polybalm cohort, there was virtually no nail damage compared to more than half suffering significant damage and distress in the placebo group. The patients in the polybalm group who still had moderate damage also suffered from other severe chemotherapy complications including neutropenic sepsis, diarrhoea and peripheral neuropathy. More precisely the DLQQ deteriorated by average of 6.10 points in the placebo group and only by 0.034 points in the polybalm group. Using the unpaired t-test with a significance level of α = 0.05 at 95% the difference was highly significant (p<0.0001). Likewise the physician recorded data revealed an average drop of 5.71 point in the placebo group and no change in the polybalm group. There were no reported balm related adverse toxicities although one patient in the plant balm group discontinued use before the end of the her first cycle quoting time constraints as the reason for stopping.
Conclusion:
The polyphenol rich essential oils and plant-based waxes in this nail bed balm profoundly reduced chemotherapy related nail damage and improved nail related quality of life compared to a plain petroleum based balm. The 180 fold improvement in nail related quality of life will be welcomed by patients suffering this unwelcome toxicity which would otherwise significantly effect up to half of people receiving chemotherapy. The precise mode of action of this investigational balm would require further evaluation to elucidate.
Appendix:
1. Quality assurance and logistics:
This non-commercial study was audited to comply with good clinical practice guidelines and Cambridge University Central Research Ethics Committee approval. It was registered with the Health Research Authority. The balms were made for this study by Power Health Ltd and European product cosmetic test were performed and are fully comply with European Union Cosmetics Standards (ref: 76/768/EEC). No member of the research team received payments to recruit patients into the study. Although this was a scientific evaluation, the FDA and MHRA classed them as a cosmetic, not licensed medicines so cannot be recommended for any medical condition or claim health benefits. The investigation balm should not be considered as an alternative medical treatment and should not be used against medical advice. The protocol was in the public domain and the balm, named after the clinical trial, is now distributed by an independent organization (via polybalm.com) which has no connection to the trials unit.
2. Further information on the polybalm trial.
The full background, protocol, design, rationale for the chosen ingredients and the ASCO presentation are available on the trial website: www.cancernet.co.uk/polybalm.htm
3. References:
- Thomas R et al. A double blind, placebo controlled randomised trial evaluating the effect of a polyphenol rich whole food supplement on PSA progression in men with prostate cancer The UK Pomi-T study. Prostate Cancer and Prostatic diseases. 2014, 17, 180-6 .
- Thomas R et al. Phytochemicals in cancer prevention and management? BJMP, 2015;8, 2
- Thomas R et al. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review Br J Sports Med: Dec 2016. doi: 10.1136/bjsports-2016-096343
- Du H et al. Fruit consumption in relation to incident diabetes and diabetic complications. 2017 doi.org/10.1371/journal.pmed.1002279
- Zhu Y et al. Dietary patterns and colorectal cancer recurrence and survival: a cohort study. BMJ Open (2013), 3(2), e002270.
- Shen CL et al Dietary polyphenols and mechanisms of osteoarthritis. J Nutr Biochem. 2012;23(11):1367-77. doi: 10.1016/j.jnutbio.2012.04.001.
- Delaquis P et al: Antimicrobial activity of essential oils. Int J Food Microbiol 74(1-2):101-9, 2002
- Smith-Palmer A et al: Antimicrobial plant essential oils. Applied Microbiol 26(2):118-22, 2002
- Baratta et al: Antimicrobial & antioxidant of essential oils. Flavour & Frag J 13(4):235-44, 2001
- Minisini AM et al: Taxane-induced nail changes. Ann Oncol 14:333-337, 2003
- Battegay EJ: Angiogenesis: Mechanistic insights. J Mol Med 73:333-346, 1995
- Wasner G et al: Docetaxel-induced nail changes: J Neurooncol 58:167-174, 2002
- Ding P & Thomas R: Solution for docetaxel onycholysis. Clin Focus Can Med 2(1):18-19, 2010
- Scottie F et al: Frozen glove to prevent docetaxel-induced onycholysis. JCO 23 (19): 4424-29, 2005
- Ishiguro H et al: Freezing for docetaxel-induced nail toxicity. Sup Care Can 20:2017-2024, 2012