Nail Toxicity Research Articles

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.

10108 Background: Onycholysis and other nail toxicities occur in approximately 20-30% of breast cancer(BC) patients receiving docetaxel(D) chemotherapy. Onycholysis, the separation of the nail plate from nail bed, is also often associated with painful paronychia decreasing patients’ the efficacy of a hydrating nail solution (EVONAIL solution, Evaux Laboratories, France) for the prevention and treatment of D-induced onycholysis and nail toxicities. Methods: This study is a prospective randomized controlled study of hydrating nail solution for prevention or treatment of onycholysis in patients with BC receiving neo/adjuvant 3-weekly D after doxorubicin plus cyclophosphamide. In experimental arm, each patient painted hydrating nail solution on nails and periungual areas once a day till developing onycholysis grade 2 or more. After Gr 2 onycholysis development, patients painted EVONAIL twice a day regardless of treatment arms. The primary endpoint is the incidence of onycholysis Gr 2 or more and recovery rate from Gr2 onycholysis. The secondary endpoints include: the incidence of all grade onycholysis; duration from first docetaxel treatment until onycholysis symptom appearance; degree of pain from nail toxicities; the incidence of other nail toxicities. Results: Since Aug 2015 to May 2016, 103 patients were enrolled and completed this study (Experimental arm(E) : 51, control arm(C): 52). Of 103 patients, 25 cases of Gr1 and 22 of Gr2 onycholysis were observed (Gr1 and 2(n,(%)) : 8(15.7%) and 7(13.7%) in E, 17(32.7%) and 15(21.4%)in C, respectively). Hydrating nail solution resulted in statistically significant reduction of Gr2 onycholysis compared to C (HR = 0.39, 95% CI 0.16, 0.96; P = 0.041) and all grade onycholysis decreased in experimental arm with statistical significance (HR = 0.37, 95% CI 0.20-0.69, P = 0.002). However, the effect of onycholysis treatment was not observed. Conclusions: Hydrating nail solution significantly reduced the incidence of D induced onycholysis in BC patients (NCT02670603). Clinical trial information: NCT02670603.

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.

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. 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. 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). Hydrating nail solution significantly reduced the incidence of docetaxel-induced onycholysis in BC patients (NCT02670603).

Efficacy of cryotherapy in paclitaxel-induced nail toxicity: Final results from a Phase II Clinical Study

Efficacy of cryotherapy in paclitaxel-induced nail toxicity: Final results from a Phase II Clinical Study

Dermatological adverse events with taxane chemotherapy.

Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel.

H02* - Efficacy of cryotherapy in paclitaxel-induced nail toxicity: preliminary results from a Phase II clinical study

H02* - Efficacy of cryotherapy in paclitaxel-induced nail toxicity: preliminary results from a Phase II clinical study

M05* - Efficacy of cryotherapy in paclitaxel-induced nail toxicity: sperimental study Phase II

M05* - Efficacy of cryotherapy in paclitaxel-induced nail toxicity: sperimental study Phase II

Cold-induced vasoconstriction for preventing onycholysis during cancer treatment

Chemotherapy induced nail toxicity is observed in up to 88 % of cancer patients. Onycholysis, a severe form of nail toxicity in which the nail is detached from the nail bed, is observed in 0 % to 44 % of cancer patients undergoing a taxanes based chemotherapy. The use of ice gloves may reduce incidence rates for chemotherapy induced onycholysis, but cause cold and pain. In this research it was hypothesized that the use of local active cooling would reduce blood flow in the distal phalanxes, whilst inducing less discomfort as compared to an ice glove.

Nail Toxicity Induced by Cancer Chemotherapy Patients: Data from the Two Multispecialty Hospital

Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems. The objectives of our study is to assessed the nail toxicity induced by cancer chemotherapy in outpatient clinical setting of two multispecialty hospital. This is a prospective observational study for a period of 12 months. Clinical variables included type of cancer, stage, treatment modalities and type of skin toxicity. Skin toxicities were graded by a dermatologist according to the National Cancer Institute Common Toxicity Criteria (NCICTC), version 3. We included all patients age (more than 16 yrs) attending oncology clinic for a period of 24 weeks. The patients with a history of cutaneous reactions, nail changes and other adverse effects. Our results shows that (Male/Female, 08/92) with Male to Female ratio of 0.08:1 who were treated with chemotherapy. The mean age of our study population was found to be 49.47±11.59 years. However, 58(58%) were from rural background and 42(42%) from urban areas. Whereas, 65% patients were farmers and 09%, Private employee. Most of the belongs to Hindu religion (62%). Our study conclude that a significant nail changes with AC-T (Cyclophosphamide Doxorubicin followed by Paclitaxel) and alopecia with FAC (5-fluorouracil Cyclophosphamide doxorubicin) are the most commonly seen adverse event in cancer patients.

Presentation and management of docetaxel-related adverse effects in patients with breast cancer

The taxane chemotherapeutic agent docetaxel has been utilized in the management of breast cancer in the adjuvant, neoadjuvant and metastatic setting. Although well tolerated by the majority of patients, docetaxel toxicity may limit the dose which can be administered. Adverse events include infusion reactions, febrile neutropenia, fatigue, fluid retention, pneumonitis, cutaneous and nail toxicity, epiphora and lacrimal duct stenosis, gastrointestinal complications, and neuropathies. In this review, we explore these complications and how they can be effectively managed to improve patient quality of life during and following docetaxel therapy.

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

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. 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. 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. 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.

Abstract P3-13-07: A-TaXel: Multicenter phase II combination of bevacizumab (A) with weekly paclitaxel (Ta) and capecitabine (Xel) in first line treatment for patients with triple negative metastatic or locally advanced breast cancer (TNMBC), a GINECO study

Abstract Background: Weekly paclitaxel and capecitabine intermittent regimen is a safe and effective combination in first line treatment of MBC including triple negative cancer (Lortholary et al, Breast Cancer Res Treat 2012). In TNMBC, the combination of A with first line Ta or Xel has been shown to improve response rate (RR) and progression-free survival (PFS) (Miller K et al., N Engl J Med 2007, Robert J et al., J Clin Oncol 2011). This phase II study is to evaluate the efficacy and safety of A-TaXel combination in TNMBC. Methods: Patients (pts) with measurable TNMBC were treated in first line until progression with q28 cycles of Ta (80 mg/m2 D1, 8, 15) + Xel (800 mg/m2 bid D1-5, 8-12, 15-19) + A (10 mg/kg D1, 14). Primary end point was best overall RR; secondary were safety, PFS, response duration and overall survival (OS). Results: From 04/2010 to 03/2012, 64 pts were accrued including 2 ineligible pts. Patients characteristics were: median age (56.7 yrs), ECOG PS 0 (55%), histological grade III (61%), previous adjuvant chemotherapy (74%), visceral disease (65%), > 1 metastatic sites (74%). Patients received a median of 6 cycles (1-6), mean 5.1. Grade 3-4 neutropenia, anemia and thrombopenia were 23%, 4% and 16% respectively with febrile neutropenia in 5% of pts. G-CSF support was observed in 7% of cycles. Most frequent non hematologic toxicities were alopecia (gr2 40%), hand-foot syndrome (gr2 27%, gr3 13%), nail toxicity (gr2 40%), hypertension (gr3 35%), neuropathy (gr2 26%, gr3 6%), mucositis (gr2 16%, gr3-4 9%), fatigue (gr3 18%, gr4 2%), nausea (gr2 15%, gr3 2%) and thrombosis (gr2 3%, gr3-4 5%). Treatment interruption due to toxicity was 22%, DPD deficiency in one patient, hospitalization 23%. RR was 77%, CR 19%, PR 58%, stable disease 14% and progressive disease 9%. Median response duration was 5.6 months. Median PFS was 7.9 months (6.7-9) and OS 19.2 months (17.3-21.1). Conclusion: A-TaXel is an effective regimen with high RR and manageable toxicity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-07.

Nail Toxicity Associated With Paclitaxel Treatment for Ovarian Cancer

A 57-year-old woman named C. B. began experiencing abdominal pain and bloating. She presented to her primary physician with these symptoms, and her physician palpated an adenexal mass on pelvic examination. That prompted a computed tomography (CT) scan of the abdomen and pelvis, which demonstrated omental thickening as well as a mildly enlarged left ovary. After initial consultation with a gynecologic oncologist, C. B. was taken to surgery and a total abdominal hysterectomy bilateral salpingo-oophorectomy omentectomy partial bowel resection, and pelvic and periaortic lymph node dissection were performed. C. B. was diagnosed with stage IV ovarian cancer involving the omentum, pelvic lymph nodes, and bowel wall and was subsequently referred for postoperative chemotherapy.

Subungueal Haemorrhages Following Docetaxel (Taxotere) Treatment

Docetaxel belongs to the taxane group of chemotherapeutic agents used in the management of various malignant diseases. Nail changes as a complication of such treatment are observed in about 44%. Subungual haemorrhages (SH), are very rare following docetaxel therapy and only a few cases have been previously reported. An 80-year-old man suffering from prostate adenocarcinoma was treated with a 3-weekly cure of docetaxel started 3 months earlier. Nail changes occurred after the 5th cycle of docetaxel. Clinical examination revealed orange discoloration of the nail plates, subungueal haemorrhages (SH) and onycholysis involving nails of all the digits and toenails of both hands and feet. These features were highly suggestive of nail toxicity following docetaxel therapy. Nail changes secondary to Taxane chemotherapy includes nail bed dyschromia, onycholysis, red or orange Beau's lines and subungueal hyperkeratosis. SH, as reported in this case, is related to the cumulative dose of docetaxel and should not be attributed to other systemic diseases. Clinicians should recognize this complication to avoid abusive treatment or investigations and inform the patients about the possibility of nail changes secondary to taxane drugs.

Weekly docetaxel in patients with metastatic breast cancer: A Bangladeshi perspective.

e11533 Background: Docetaxel has demonstrated high antitumor activity in first and second line treatment of metastatic breast cancer. Usually it is administrated three weekly at a dose of 75mg/ m2. We evaluated the efficacy and toxicity of Docetaxel in metastatic breast cancer in weekly bases. This study analyzed the efficacy and toxicity of docetaxel given weekly. Methods: Thirty eight patients with metastatic breast cancer received docetaxel, 35 mg/m2 weekly for six weeks, followed by two weeks interval. Additional cycles (three weeks' treatment, two weeks' rest) were given until disease progression or death. All patients had received prior chemotherapy. Of them 32 patients previously received anthracycline-containing regimens and 5 patients had received taxane based regimens. Results: Out of thirty eight patients thirty seven were evaluable. There was one complete response (3%), 11 patient has partial responses (30%), 17 patients with stable disease (46%) and six with disease progression (16%). Overall response rate was 78%. Median progression-free survival was 9.2 months. Three patients showed grade 3 neutropenia. 14 showed grade 3 alopecia, and various grade 1–2 non-haematological toxicities were observed. Treatment was delayed in two patients due to haemalotoxicity and stopped in one patient due to painful nail toxicity. Conclusions: Docetaxel is effective in three weekly regimens. In our study we found weekly docetaxel is as effective as the previous regimen. The efficacy of weekly docetaxel (35 mg/m2) can be an effective schedule for metastatic breast cancer who has received chemotherapy previously. The toxicity in this regimen is very low and manageable.

Capecitabine and weekly paclitaxel as first-line therapy in Thai patients with metastatic breast cancer

The combination of a taxane and capecitabine offers synergistic antitumor activity. This study aimed to determine the efficacy and tolerability of a paclitaxel and capecitabine combination in Thai patients with metastatic breast cancer (MBC) not previously treated for metastatic disease. This open-label, single-center, non-comparative phase II study was conducted between December 2006 and March 2009. In all 40 MBC patients were treated with oral capecitabine 1000 mg/m(2) twice daily on days 1 to 14, and weekly paclitaxel 80 mg/m(2) in a 3-week cycle for a total of six cycles. After a median follow up of 13.4 months, an overall objective response rate of 80%, with a partial response of 74% and a complete response of 5% were achieved. While 8% of patients achieved stable disease, 13% had progressive disease. Median time to progress was 8 months and median overall survival was 24.4 months. One patient discontinued because of hypersensitivity to paclitaxel. There was no grade 4 toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade 2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3), neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both of which 5% experienced grade 1 severity). A first-line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.

The risk of nail changes with epidermal growth factor receptor inhibitors: A systematic review of the literature and meta-analysis

The overall incidence and risk of nail changes associated with the use of epidermal growth factor receptor inhibitors (EGFRIs) varies widely across the literature. We conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing nail toxicity among patients receiving EGFRIs. Databases from Pubmed and Web of Science from January 1998 until July 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through July 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of nail toxicity were calculated using random-effects or fixed-effects model depending on the heterogeneity of the included studies. A total of 2107 patients from 22 clinical trials were included in this analysis. The overall incidence of all-grade nail toxicity was 17.2% (95% confidence interval [CI]: 13.8%-21.3%), with an RR of 76.94 (95% CI: 40.76-145.22, P < .001). The overall incidence of high-grade nail toxicity was 1.4% (95% CI: 0.9%-2.1%), with an RR of 13.11 (95% CI: 3.73-46.03, P < .001). The ability to detect and grade nail changes may vary among institutions. There is a significant risk of developing nail toxicity in cancer patients receiving EGFRIs. The risk is independent of the underlying agent. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing of EGFRI.

Pneumatosis Intestinalis After Cetuximab-containing Chemotherapy for Colorectal Cancer

Cetuximab, a chimeric monoclonal antibody to epidermal growth factor receptor, is an effective chemotherapeutic agent for patients with metastatic colorectal cancer. Whereas several specific adverse reactions to cetuximab such as skin rash and nail toxicity have been reported, there have been few reports of pneumatosis intestinalis related to cetuximab-containing chemotherapy. We describe here three patients with colorectal cancer who developed pneumatosis intestinalis during treatment with cetuximab-containing chemotherapy, which developed after 7, 19 and 47 weeks of cetuximab treatment, and discovered on routine follow-up computed tomographic scans for response evaluations. None of these patients complained of abdominal pain, showed signs of peritoneal irritation on physical examination or had elevated serum concentrations of acute inflammatory markers. Following cessation of cetuximab and conservative medical treatment, all three patients showed complete resolution of pneumatosis intestinalis on abdominal pelvic computed tomographic scans.

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

PurposeThe 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. MethodsThis 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. ResultsThe 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. ConclusionsThe 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.

Quality of life in patients with dermatologic toxicities: Experience from the SERIES clinic.

9104 Background: Anti-cancer therapies such as radiation, cytotoxic chemotherapy, and novel targeted agents may cause a range of dermatologic toxicities (dTs). At present, there are limited data regarding the impact of dTs on dermatologic quality of life (dQoL). We systematically investigated their impact on dQoL in patients seen at the SERIES clinic, a referral center for management of dTs stemming from anti-cancer therapies. Methods: Medical records of patients seen in the dermatology referral clinic for cancer patients at Northwestern University between 9/2007 and 9/2008 were searched for completion of Skindex-16, a dermatology-specific QoL questionnaire. Skindex scores range from 0 (best QoL) to 96 (worst QoL) and measure 3 domains: symptoms, emotions and function. The impact of dTs on the total Skindex score and the scores of each domain were analyzed. Descriptive statistics (means, medians, range) were used to describe scores. Differences in mean scores were evaluated by linear regression. Results: A total of 425 patients were analyzed. EGFRI-associated papulopustular (ppr) rash, HFS/HFSR, nail toxicities, xerosis, fissures, pruritus and alopecia were observed in 26.7%, 12.5%, 9.2%, 31.1%, 5.0%, 18.1%, and 9.4% of patients, respectively. The presence of ppr rash was associated with a greater impact on the mean total, symptoms, emotions, and function domain scores as compared to patients without ppr rash (45.1 vs. 30.4; 11.6 vs. 8.4; 23.4 vs. 16.5; 10.1 vs. 5.6, p<0.001). Similarly, the presence of pruritus was associated with a greater impact on the mean total and all three domains scores (46.5 vs.31.6; 13.5 vs. 8.3; 23.2 vs. 17.2; 9.8 vs. 6.2, p<0.001, =0.003, =0.0008, respectively). Patients (n=32) with ≥ 3 dTs (ppr rash, nail toxicities, xerosis, fissures, and pruritus) had a significantly higher mean total as well as symptoms, emotions and function scores as compared to patients with fewer dTs (47.6, 14.4, 23.4, 9.8, respectively, p<0.001). Conclusions: dTs are associated with diminished dQoL; ppr rash and pruritus appear to have the greatest negative impact. Future emphasis should be placed on developing effective management strategies for dTs in order to minimize the likelihood of reduced dQoL.

BLUE-BLACK DISCOLORATION OF THE NAILS ASSOCIATED WITH GEFITINIB

Blue-black discoloration appeared on all fingernails in a 57-year-old woman after 3 weeks of gefitinib 250mg once daily for her locally advanced lung cancer (Figure 1 & 2), and it could not be removed by solvents, such as alcohol. The nails did not become thickened or atrophic, and adjacent skin was normal. During the period of treatment, no exposure of other significant drug insult was noted. Gefitinib is a small molecular tyrosine kinase inhibitor blocking the epidermal growth factor receptor (EGFR) pathway (1, 2). The most frequent cutaneous manifestation is a papulopustular eruption varying from 24% to 62% of patients on gefitinib in clinical trials, followed by nail changes, including painful paronychial inflammation, ingrown nails and xerosis. Approximately 10% to 15% of patients have nail toxicity between 4 and 8 weeks after initiation of treatment (1). However, blue discoloration or pigmentation of nails is rarely associated with gefitinib in previous literature. In contrast to skin rash, resolving within 4 weeks after cessation of EGFR pathway inhibitors, nail toxicity can be persistent for several months after withdrawal (2). Nevertheless, the mechanism is still unknown (1, 2). Blue-black discoloration can occur in the nail plate, vascular nail bed or the lunula, and pigmentation is usually related to drugs, such as minocycline, zidovudine and antimalarial drugs. In certain circumstances, however, we have to pay attention, as blue lunula can also be a marker of more serious diseases, such as argyria, Wilson’s disease and congenital diseases including haemoglobin M disease and hereditary acrolabial telangectasia (3).