Mild Cryotherapy for Prevention of Paclitaxel-Induced Nail Toxicity in Breast Cancer Patients: A Phase II Single-Arm Clinical Trial.

BACKGROUND: Nail changes are among the most common dermatological adverse events in paclitaxel-receiving patients. Although effective, low-temperature prophylactic cryotherapy is discomforting and a potential cause of side effects, resulting in low patients' adherence. PATIENTS AND METHODS: A phase II single-arm study evaluating mild cryotherapy for the reduction of 12-week, grade 2 nail toxicity was conducted on 67 taxane-naïve breast cancer patients (age 18-74 years) undergoing weekly adjuvant chemotherapy with paclitaxel. Instant-ice packs were fixed over the fingers and toes for a total of 70 minutes during paclitaxel infusion at a temperature between -5 °C and +5 °C. Nail toxicity was evaluated weekly (CTCAE vs 4.03), including grade 2 (ie, onycholysis, subungual hematoma, onychomadesis) and grade 1 nail toxicities. RESULTS: Twelve patients experienced grade 2 nail toxicities (17.9%, 95% confidence interval [CI] 9.6%-29.2%; median time to onset: 56 days): onycholysis was the most frequent grade 2 toxicity (13.4%), followed by subungual hematoma (9.0%) and onychomadesis (1.5%). Grade 1 toxicity occurred in 33 patients (63.5%, 95% CI 49.0%-76.4%) with nail discoloration representing by far the most frequent toxicity (59.6%). Seventeen patients (25.4%) reported no nail toxicity. 62.7% of patients reported no pain and 22.4% suffered moderate pain. No patient experienced severe pain or others adverse effects. CONCLUSIONS: Instant-ice pack is a feasible prophylactic intervention for nail toxicity, well tolerated by patients and with limited impact on routine workload. It could be considered for patients refusing (or interrupting) cryotherapy, and it can be implemented when frozen gloves management is not feasible.

A Timeline of Onychomycosis Therapy and Future Directions.

Onychomycosis was first described in the mid-1800's, and early treatment regimens involved applying corrosive substances and nail plate avulsion. It was not until the mid-1900's that more specific antifungal agents were utilized. Initially, only oral drugs were used, with ciclopirox 8% solution later approved in 1999. Presently, terbinafine, itraconazole, and fluconazole (off-label) are used for systemic onychomycosis therapy in the US, and topicals include ciclopirox, efinaconazole and tavaborole. Devices, topicals with new mechanisms of action, and oral medications with potentially better efficacy are now being explored for treatment of onychomycosis.

Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. RESULTS: We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. CONCLUSIONS: Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Importance of Sock Type in the Development of Foot Lesions on Low-Difficulty, Short Hikes.

Background and objectives: Foot lesions can be developed during hiking because of external factors. This makes it important to study the effect of hiking equipment on lesion development. Materials and Methods: Technical and non-technical socks were given to 109 hikers to wear during a short hike. Participants were examined at three stages of the hike to determine the development of dermal, muscle and nail lesions, temperature and perimeter in various areas of each foot. Results: The percentage of hikers without injuries was significantly higher among those wearing technical socks (p-value < 0.001). Differences were also observed in mean foot temperature, which was higher in participants wearing technical socks (p-value < 0.001). Conclusion: The results indicate that even on a low-difficulty, short-term sport activity, it is advisable to wear technical socks to prevent lesion development and keep the foot temperature more stable. Sock type was identified as an external conditioning factor in lesion development.

Treatment and prevention of paronychia using a new combination of topicals: report of 30 cases.

AIM: Moderate and chronic paronychia is a common disease affecting the hand. Treatment can be effective but the affection is often recurrent, especially as an occupational disease. Moreover, this condition may be complicated by a Candida spp or by bacterial infections. Therefore, general preventive measures can be useful in maintaining health. The aim of this study was to investigate the efficacy and tolerability of a new combination of topical medications in the treatment and prevention of moderate and chronic paronychia. This formulation includes an insulating polymer (Syn-cell barrier), two topical antifungals (octopirox and climbazole) and a molecule with anti-inflammatory activity (corticoid-like repair). METHODS: Thirty adult subjects (age, 16-78 years; 24 females and 6 males) affected by moderate or chronic paronychia, with or without nail alterations, were evaluated. Included in the study were patients with allergic contact dermatitis (8), irritant contact dermatitis (19), psoriatic paronychia (2 patients), lichen planus of the nails (1 patient). Sometimes Candida spp or bacteria overlapped with paronychia (16 patients positive for Candida spp and 4 patients with bacterial paronychia), sometimes infectious paronychia was not associated with dermatitis of the hands. All 30 subjects were treated with a new cream formulation, three applications per day for 2 months. In 8 patients with proven and severe candidiasis of the nails, oral fluconazole 100 mg was added for 20 days. All patients with bacterial perionyxis took clarithromycin 500 mg twice daily for six days. Patients were then followed for 8 weeks. RESULTS: After two months of treatment, 26 patients responded to therapy. In particular, the treatment evaluation at the end of the follow-up period showed a clinical cure in 46.6% (14 patients), improvement in 40% (12 patients), and failure in 13.4% (4 patients). There was a side effect (moderate skin irritation) in 2 patients, but the drug was not discontinued. CONCLUSION: Results of the present study, based on its safety, effectiveness and innovative features, indicate that this combination of topical cream may be considered as a new alternative for treatment and prevention of paronychia, especially in case of occupational hand disease where prolonged treatment and continuous prevention are needed.

Cryotherapy for docetaxel-induced hand and nail toxicity: randomised control trial.

PURPOSE: This study investigated the efficacy and safety of cryotherapy, in the form of frozen gel gloves, in relation to docetaxel-induced hand and fingernail toxicities. PATIENTS AND METHODS: After piloting with 21 patients, a consecutive series sample of patients (n=53) prescribed docetaxel every 3 weeks, for a minimum of three cycles, was enrolled in this randomised control trial. Participants acted as their own control, with the frozen gel glove worn on one randomised hand for 15 min prior to infusion, for the duration of the infusion, and for 15 min of after completion of treatment. Hand and nail toxicities were evaluated by two blinded assessors according to CTCAE.v4 criteria. To assess the potential for cross-infection of multi-use gloves, microbial culture and sensitivity swabs were taken of each glove at every tenth use. RESULTS: Of the 53 participants enrolled in the main study, 21 provided evaluable data. There was a 60 % withdrawal rate due to patient discomfort with the intervention. The mean incidence and severity of toxicities in all evaluable cycles in control and intervention hands respectively were erythroderma grade 1 (5/5 %), nail discolouration grade 1 (81/67 %), nail loss grade 1 (19/19 %) and nail ridging grade 1 (57/57 %). No significant differences were determined between hand conditions in terms of time to event, nor in terms of toxicity in gloved and non-gloved hands. CONCLUSION: While cryotherapy in the form of frozen gloves for the cutaneous toxicities associated with docetaxel is safe, its limited efficacy, patient discomfort and some logistical issues preclude its use in our clinical setting.

Degree of freezing does not affect efficacy of frozen gloves for prevention of docetaxel-induced nail toxicity in breast cancer patients.

PURPOSE: Frozen gloves (FG) are effective in preventing docetaxel-induced nail toxicity (DNT), but uncomfortable. The preventive effect of FG for DNT was compared using a standard (-25 to -30°C) or more comfortable (-10 to -20°C) preparation. METHODS: Breast cancer patients receiving docetaxel were eligible. Each patient wore an FG (prepared at -10 to -20°C for 90 min) for 60 min without replacement on the right hand. The left hand was protected by standard methods (FG prepared at -25 to -30°C overnight and worn for 90 min with replacement at 45 min). The primary endpoint was DNT occurrence at 5 months. Secondary endpoints included docetaxel exposure [cumulative dose and area under the blood concentration time curve (AUC)] until DNT occurrence and discomfort from FG. The pharmacokinetics of docetaxel was assessed. RESULTS: From 23 patients enrolled between December 2006 and June 2010, seven who received docetaxel for less than 5 months were excluded from evaluation. The median accumulated docetaxel dose was 700 mg/m(2) (340-1430 mg/m(2)). Within 5 months of FG use, none developed protocol-defined DNT in either hand. Two patients (13%) developed DNT at 7.2 and 7.3 months, respectively, both at -10 to -20°C. In the control hand (-25 to -30°C), discomfort occurred in 92% of the cycles, compared to 15% in the experimental hand (-10 to -20°C). Five patients (22%) experienced pain at -25 to -30°C, but none did at -10 to -20°C. The degree of docetaxel exposure was not related to DNT occurrence in our study. CONCLUSION: A convenient preparation of FG at -10 to -20°C is almost as effective as a standard preparation at -25 to -30°C, with significantly less discomfort.

Taxane-induced nail changes: Predictors and efficacy of the use of frozen gloves and socks in the prevention of nail toxicity.

PURPOSE: The primary endpoint of this study was to determine predictors of taxane-related nail toxicity. The secondary endpoint was to evaluate the efficacy of the use of frozen gloves and socks in the prevention of taxane-related nail toxicity. METHODS: This descriptive, interventional, cross-sectional study was conducted with 200 patients. The patients were assigned to the frozen gloves/socks intervention group or control group. Frozen gloves/socks were applied only in hourly taxane-based treatments. The Patients Record Forms of the clinic were used in data collection. Nail changes were graded using the NCI Common Toxicity Criteria for each patient and treatment. Logistic regression analysis was performed to predict the factors that affect nail changes. RESULTS: The majority of the patients enrolled in the study were women diagnosed with breast cancer. The two groups were statistically similar for the cancer diagnosis, type and number of taxane cycles administered. Grade 1 nail toxicity was found in 34%, grade 2 in 11%, and grade 3 in 5.5% patients. Taxane-related nail toxicity was higher in patients who were female, had a history of diabetes, received capecitabine in conjunction with docetaxel and had breast or gynecological cancer diagnosis. Nail changes increased with an increase in the number of taxane cycles administered, BMI and severity of treatment-related neuropathy. CONCLUSIONS: The multivariate analysis demonstrated that BMI, breast or ovarian cancer diagnosis and the number of taxane cycles administered were the independent factors for this toxicity. No statistically significant difference in nail toxicity incidence and time to occurrence of nail changes was found between the intervention and the control groups.

The role of certified foot and nail care nurses in the prevention of lower extremity amputation.

The primary purpose of this article is to outline the role, opportunities, and benefits of the certified foot and nail care nurse (CFCN). Current demographic trends toward an aging population and associated health issues such as diabetes mellitus, arthritis, peripheral arterial disease, dementia, and loss of visual acuity hinder self-care of the feet and nails. The resulting foot and nail care needs create opportunities for CFCN to promote health and prevent adverse outcomes such as infection and limb loss. Routine foot and nail assessment, clinically appropriate care, and individualized patient education are essential for achieving positive outcomes. Until recently, individuals had limited options for obtaining needed care and have relied on nonclinicians or podiatry appointments that may not be covered by insurance and, thus, may not be affordable. Through the CFCN certification process, nurses gain knowledge and skills to provide the care that can improve foot health for an aging population.

Docetaxel-related side effects and their management.

Docetaxel is an effective treatment approved in five key cancers, but its effectiveness in clinical practice can be compromised by sub-optimal side-effect management. The aim of this review was to investigate the extent of the published work on specific docetaxel-related side effects and to provide, where possible, evidence-based recommendations for their prevention and management. PubMed and the American Society of Clinical Oncology (ASCO) databases were systematically searched for articles published in English over the past 5 years and 2 years, respectively, and pertaining to six side effects identified as being common to the majority of docetaxel regimens and indications and of particular relevance to the oncology nurse. The Cochrane library was also searched. A total of 103 citations were identified, 14 of which discussed strategies for the prevention or management of febrile neutropenia (n=6), hypersensitivity reactions (3), fluid retention (1) and nail changes (4). No articles were identified that related to asthenia or neuropathy. Based on the literature review, evidence/guidelines-based advice for the use of G-CSF in febrile neutropenia is provided. The evidence base with respect to the other side effects does not permit the formulation of recommendations. It is the experience of the authors, however, that the severity of symptoms experienced by patients is generally mild and the side effects are for the most part easily managed with prophylactic and supportive care measures. It is, therefore, important to share and build on experiences, through research and discussion, to maximise the healthcare professional's ability to offer the best standard of care to patients.

Nail toxicity induced by cancer chemotherapy.

PURPOSE: To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management. DATA SOURCE: A search of MEDLINE and EMBASE (1966-2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references. DATA EXTRACTION: The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity. DATA SYNTHESIS: Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.