To our knowledge, this was the first RCT that investigated a range of topical interventions for taxane-induced nail changes in women with EBC whilst providing standard care advice on wearing gloves, maintaining hand hygiene and nail care, avoidance of toxic ingredients and artificial nail use. The results suggest that combined with guidance on hand hygiene and nail care, both the specialised OnicoLife ® nail drops and nail oil were associated with less nail toxicity than use of dark nail varnish. Despite asking patients to comply with the protocol before making their decision on participation, a slightly higher dropout than anticipated occurred in the NP intervention arm.
Additionally, the effectiveness of the interventions were monitored three months from the date of the participant’s final infusion, thus providing time to appraise nail growth and condition over the longer term. Therefore, longer than the commonly reported follow up period in other studies [11–13].
Owing to the greater number of categories incorporated in the NToX-G12 assessment of nails, our study also identified a pre-existing nail issues at T1 (baseline). This is in keeping with other studies . However, most of these were minor issues common to healthy individuals such as hard skin and skin hacks. Similarly, at T2, the most common and persistent changes were ridging (Beau’s lines) pitting, brittleness and white nail discolouration. Orange nail discolouration has previously been linked with haemorrhagic suffusion of the nail bed [3, 28]. In our study, it was not possible to ascertain why orange discolouration was only seen in fingernails of women from certain ethnic origins, since all participants recruited to the nail polish arm applied a base coat to prevent staining from nail polish. This may be worthy of exploration in future studies. No other dermatological concerns associated with nail products were reported.
The documentation of nail changes continues to be limited by the lack of a standardised instrument, thus leading to difficultly in comparing outcomes of previous nail interventions. The CTCAE has been previously criticised and grading of nail changes can only ever depend on the interpretation of the investigator. For example, only one oncology nurse specialist assessed all participants for nail toxicities using the CTCAE v4 in the RCT using HNS , and in the polybalm study  it was unclear how many physicians were involved in nail assessments or their area of expertise. In a real world oncology setting, consistent assessment by the same health care professional is often unrealistic; hence in our study we used a team of experienced chemotherapy and CNS nurses.
Although we addressed the development of two nail instruments for use in a clinical setting, the resulting NToX-G12 scores were in the lower range of the scale. As there were limited reports of more severe, nail changes with higher weighting such as moderate pain, infection, paronychia, or onycholysis, the relative homogeneity of the patients included in this trial may have affected the results.
To date, there have been various topical interventions investigated for the prevention of taxane associated nail changes [11–13], which have varied in methods of application for example, brushing or painting the nail. In our study, participants using both the nail oil and specialised drops experienced less nail problems than those using nail polish. Since both interventions were applied by manually massaging the product onto the nail area , we postulate it may be the massage action stimulating the vascular elements of the nail and nail matrix, thus helping ameliorate nail changes. This is in contrast with previous studies using cryotherapy, which suggest a reduction in vascular flow reduces drug exposure thus resulting in less toxicities . If this is the case, it should be considered whether it is not only the topical agent, but also the method of massaging the agent into the nail that brings about effective change, which may be assisting in lesser occurrence/severity and overall better nail health. Thus, this is a suggested area for future investigation.
The cost of any intervention needs consideration when deciding to adopt into clinical practice, especially when resource and financial savings predominate. The purchase of multiple medical devices such as frozen gloves involves a substantial initial purchase, maintenance costs plus replacement of disposable single-use components. In addition, cryotherapy involves an additional burden on healthcare resource, whereas this is the opposite for self-managed interventions.
While no statistical difference was demonstrated for quality of life over the three time points, it is suggested to have clinical significance in that none of the study interventions demonstrated superiority in affecting quality of life. This is to be the subject of a separate paper for publication.
In conclusion, the results of this trial may support clinicians to suggest alternatives for patients based on their needs and preferences and advise nail oil or specialised drops may be better than the use of dark nail polish during and several months after taxane treatment for breast cancer.
While other studies involve only ‘cosmetic’ interventions, OnicoLife ® drops, as a nail- specific medical device has shown potential to reduce nail changes and thus, may be recommended to patients. Future investigation involving larger powered, RCTs into the comparison / combination of cryotherapy and topical solutions using suitably sensitive and specific outcome measures are warranted.