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 randomised controlled trial of interventions for taxane-induced nail toxicity in women with early breast cancer.

Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of different topical interventions to ameliorate nail toxicity. Secondary aims were to explore the full range and severity of possible nail changes associated with taxane-based chemotherapy and the specific impact this had on quality of life, using two novel measures. This was an exploratory randomised controlled trial of three topical interventions (standard care, nail polish or specialist nail drops) for the prevention or reduction of nail changes induced by taxane-based chemotherapy. Outcomes included nail toxicity assessed at three time points (baseline, 3 weeks and 3 months post completion of chemotherapy) using two novel clinical tools (NToX-G12, NToX-QoL) and the Common Terminology Criteria for Adverse Events (CTCAE v3) and EQ-5D-5L. A total of 105 women were recruited (35 in each arm) and monitored up to three months post completion of chemotherapy. Almost 20% of patients were over the age of 60 years. There were 26 withdrawals, the majority from the nail polish arm. Residual Maximum Likelihood REML analysis indicated a significant arm, time and interaction effect for each intervention (p < 0.001). Less nail toxicity was observed in patients receiving specialist nail drops or standard care arms in comparison to those using nail polish. This study provides evidence to support clinicians' suggestions on nail care recommendations based on the patients' needs and preferences. Future investigations into comparing or combining cryotherapy and topical solutions that can support patient's decisions are warranted.

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.

A prospective randomized controlled trial of hydrating nail solution for prevention or treatment of onycholysis in breast cancer patients who received neoadjuvant/adjuvant docetaxel chemotherapy.

PURPOSE: Onycholysis and other nail toxicities occur in approximately 20-30% of breast cancer (BC) patients receiving docetaxel chemotherapy. Onycholysis is often associated with painful paronychia, decreasing patients' quality of life. In this study, we aimed to evaluate the efficacy of hydrating nail solution (HNS) (EVONAIL® solution, Evaux Laboratories, France) for the prevention and treatment of docetaxel-induced onycholysis and nail toxicities. METHODS: This study was a prospective, randomized, controlled study of HNS for the prevention or treatment of onycholysis in patients with docetaxel after doxorubicin plus cyclophosphamide. In the experimental arm, patients painted HNS on nails and periungual areas once a day till developing onycholysis grade 2. After grade 2 onycholysis development, patients applied HNS twice a day regardless of treatment arm. The primary endpoints were the incidence of onycholysis grade 2 and recovery rate from grade 2 onycholysis. RESULTS: From August 2015 to May 2016, 103 patients were enrolled and completed this study. Of these, 25 cases of grade 1 and 22 of grade 2 onycholysis were observed. Prophylactic application of HNS resulted in a statistically significant reduction of grade 2 onycholysis compared to controls (P = 0.001) and all grade onycholysis was also significantly lower in the experimental arm (P = 0.034). Multivariate analysis showed that HNS decreased grade 2 onycholysis (Hazard ratio (HR) 0.366, 95% confidence interval (CI) 0.148, 0.902; P = 0.029) and all grade onycholysis (HR 0.372, 95% CI 0.201-0.687, P = 0.002). CONCLUSIONS: Hydrating nail solution significantly reduced the incidence of docetaxel-induced onycholysis in BC patients (NCT02670603).

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.

Matched case-control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel-induced onycholysis and cutaneous toxicity of the foot.

BACKGROUND: Onycholysis occurs in approximately 30% of patients treated with docetaxel. The efficacy and safety of an Elasto-Gel frozen sock (FS) was investigated for the prevention of docetaxel-induced nail and skin toxicity of the feet. METHODS: Patients receiving docetaxel at a dose of 70 to 100 mg/m(2) every 3 weeks were eligible for this matched case-control study. Each patient wore an FS for 90 minutes on the right foot. The unprotected left foot acted as control. Nail and skin toxicities were assessed using National Cancer Institute Common Toxicity Criteria (version 3) and compared using a 2-sample Wilcoxon matched-pairs rank test adjusted for tied values. RESULTS: Fifty consecutive patients were included between April 2005 and January 2007. Nail toxicity was significantly lower in the FS-protected foot compared with the control foot (grade 0: 100% versus 79%; and grade 1 and 2: 0% versus 21%, respectively) (P= .002). Skin toxicity was grade 0: 98% versus 94%; and grade 1 and 2: 2% versus 6% in the FS-protected and the control feet, respectively. The median times until toxicity occurrence were not found to differ significantly between the groups. One patient experienced discomfort because of cold intolerance. CONCLUSIONS: Cold therapy using FS significantly reduced the incidence of docetaxel-induced foot nail toxicity, as previously demonstrated using frozen gloves for the hands.