Toxicological assessment of minoxidil: A drug with therapeutic potential besides alopecia.

Minoxidil is regularly prescribed for alopecia, and its therapeutic potential has expanded in recent times. However, few studies have been conducted to evaluate its toxicity, and controversial findings regarding its mutagenic activities remain unsolved. This study aimed to access cytotoxic, genotoxic, and mutagenic properties of minoxidil using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, comet assay, and micronucleus test in mouse fibroblast (L929) cells and its point mutation induction potential in the Salmonella/microsome assay. Furthermore, an in vivo toxicity assessment was conducted in Caenorhabditis elegans. Minoxidil showed cytotoxicity at 2.0 mg/mL in MTT assay. Genotoxicity was observed after 3 h treatment in L929 cells using comet assay. No mutagenic effect was observed in both the micronucleus test and the Salmonella/microsome assay. The lethal dose 50 in C. elegans was determined to be 1.75 mg/mL, and a delay in body development was detected at all concentrations. In conclusion, minoxidil induces DNA damage only in early treatment, implying that this DNA damage may be repairable. This observation corroborates the absence of mutagenic activities observed in L929 cells and Salmonella typhimurium strains. However, the toxicity of minoxidil was evident in both C. elegans and L929 cells, underscoring the need for caution in its use.

Ethical, legal, organizational and social issues related to the use of scalp cooling for the prevention of chemotherapy-induced alopecia: A systematic review.

INTRODUCTION: Scalp cooling (SC) aims to prevent chemotherapy-induced alopecia. The goal of this systematic review is to tackle ethical, legal, organizational and social issues related to SC. METHODS: A critical appraisal of the literature was carried out using a systematic review design. MEDLINE, Embase and Web of Science databases were searched up until 2 June 2021. Studies addressing these aspects in English or Spanish were considered. Representatives of both patient associations and professional scientific societies related to the topic participated in the design of the protocol and the review of the findings. RESULTS: A total of 17 studies were included. Articles were critically appraised using the MMAT and SANRA. Findings were organized into four categories: (1) ethical aspects focused on equal access, gender equity and doctor-patient communication supported by Patient Decision Aids (PtDAs); (2) patient perspective and acceptability; (3) professional perspective and acceptability; (4) organizational aspects focused on accessibility and feasibility. CONCLUSION: Cancer patients' expectations when using SC need to be adjusted to reduce the potential distress associated with hair loss. PtDAs could help patients clarify their values and preferences regarding SC. Equal access to technology should be guaranteed. PATIENT OR PUBLIC CONTRIBUTION: In this systematic review, the representatives of the patient associations (Ms. María Luz Amador Muñoz of the Spanish Association Against Cancer [AECC] and Ms. Catiana Martinez Cánovas of the Spanish Breast Cancer Federation [FECMA]) participated in the review of the study protocol, as well as in the results, discussion and conclusions, making their contributions. In the type of design of these studies (systematic reviews), it is not usual to have the direct participation of patients, but in this one, we have done so, as it is a systematic review that is part of a report of the Spanish Network of Health Technology Assessment Agencies (ETS).

Geographic disparities in access to scalp cooling for the prevention of chemotherapy-induced alopecia in the United States.

BACKGROUND: Chemotherapy-induced alopecia is psychologically challenging for patients undergoing cancer treatment, and scalp cooling has been shown to prevent or decrease the hair loss. OBJECTIVE: To evaluate whether access to scalp cooling varies by geographic area in the United States. METHODS: Cancer treatment centers offering scalp cooling were identified using data from the Rapunzel Project. Medicare claims data were queried to evaluate the number of chemotherapy infusions occurring in each zip code in the United States. Geographic distribution of chemotherapy infusions and scalp cooling centers was determined using ArcGIS software. The average distance from the geographic center of all 5-digit zip codes in which chemotherapy infusions occur to the nearest scalp cooling center was calculated in miles. RESULTS: There are 366 chemotherapy infusion centers in the United States that offer scalp cooling. Overall, 43.9% of Medicare-billed chemotherapy infusions in the United States occur in zip codes less than 12.5 miles from a scalp cooling center, 24.8% occur between 12.5 and 49.9 miles away, and 31.3% occur more than 50 miles away. LIMITATIONS: Our results are only generalizable to patients seen at Medicare-accepting institutions in the United States. CONCLUSIONS: Geographic disparities affect which patients can access scalp cooling therapy, and implementation in suburban and rural areas would increase access for patients who wish to preserve their hair while undergoing chemotherapy.

A Chinese version of the chemotherapy-induced alopecia distress scale based on reliability and validity assessment in breast cancer patients.

PURPOSE: Chemotherapy-induced alopecia is a common and emotionally traumatic side effect on breast cancer patients. In order to make up for the deficiency of measuring tools in China, our study aims at translating the chemotherapy-induced alopecia distress scale (CADS) into Chinese and evaluating the psychometric properties of the Chinese version of CADS (CADS-C) in breast cancer patients. METHODS: The validity and reliability of CADS-C were measured by a questionnaire survey among 301 breast cancer patients from Chinese mainland. Construct validity was assessed through factor analysis and contrasted group comparisons. The validity of the content was examined by an experts group. The internal consistency and test-retest reliability were evaluated by calculating Cronbach's alpha and the intraclass correlation coefficient. RESULTS: The content validity index was 0.94; a structure with three factors was revealed by exploratory factor analysis which explained 65.40% of the variance and proved by confirmatory factor analysis. The contrasted group comparisons showed significant differences among different degrees of alopecia. The average variance extracted and composite reliability and correlations between CADS and body image, quality of life and self-esteem proved the convergent validity. The Cronbach's alpha and the intraclass correlation coefficient of the total scale were 0.90 and 0.89 respectively, indicating satisfactory internal consistency and time stability. CONCLUSION: The scale appears to be a reliable and valid tool to measure chemotherapy-induced alopecia distress among breast cancer patients in China.

Assessment of Quality of Life and Treatment Outcomes of Patients With Persistent Postchemotherapy Alopecia.

Importance: Persistent alopecia occurs in a subset of patients undergoing chemotherapy, yet the quality of life (QOL) of these patients and their response to therapy have not been described in a large patient cohort. Objective: To characterize the clinical presentation of patients with persistent chemotherapy-induced alopecia (pCIA) or endocrine therapy-induced alopecia after chemotherapy (EIAC) and their QOL and treatment outcomes. Design, Setting, and Participants: A retrospective multicenter cohort of 192 women with cancer treated with cytotoxic agents who received a clinical diagnosis of persistent alopecia (98 with pCIA and 94 with EIAC) between January 1, 2009, and July 31, 2017, was analyzed. All patients were from the dermatology service in 2 comprehensive cancer centers and 1 tertiary-care hospital. Data on demographics, chemotherapy regimens, severity, clinical patterns, and response to hair-growth promoting agents were assessed. Data from the Hairdex questionnaire were used to assess the QOL of patients with alopecia. Main Outcomes and Measures: The clinical presentation, response to dermatologic therapy, and QOL of patients with pCIA were assessed and compared with those of patients with EIAC. Results: A total of 98 women with pCIA (median age, 56.5 years [range, 18-83 years]) and 94 women with EIAC (median age, 56 years [range, 29-84 years]) were included. The most common agents associated with pCIA were taxanes for 80 patients (82%); the most common agents associated with EIAC were aromatase inhibitors for 58 patients (62%). Diffuse alopecia was predominant in patients with pCIA compared with patients with EIAC (31 of 75 [41%] vs 23 of 92 [25%]; P = .04), with greater severity (Common Terminology Criteria for Adverse Events, version 4.0, grade 2) among patients with pCIA (29 of 75 [39%] vs 12 of 92 [13%]; P < .001). A negative emotional effect was reported by both groups. After treatment with topical minoxidil or spironolactone, moderate to significant improvement was observed for 36 of 54 patients with pCIA (67%) and for 32 of 42 patients with EIAC (76%). Conclusions and Relevance: Persistent chemotherapy-induced alopecia is frequently more severe and diffuse when compared with EIAC, and both groups of patients experienced a negative effect. A modest benefit was observed with dermatologic therapy. Additional studies are warranted to develop effective strategies for prevention and effective therapy for pCIA and EIAC.

[Italian Version of Chemotherapy-induced Alopecia Distress Scale (I-CADS): linguistic cultural adaptation, content validity and psychometrics assessment.] / Versione italiana della Chemotherapy-induced Alopecia Distress Scale (I-CADS): adattamento linguistico culturale, validità di contenuto e valutazione delle proprietà psicometriche.

Distress could be often experienced by breast cancer patients with chemotherapy-induced alopecia. Those distress assessment is strategic to deliver care in a tailored way, enhancing the overall wellbeing. So far, those distress is measurable by the Chemotherapy-induced Alopecia Distress Scale (CADS), which is not yet available in Italian, due to there are no validation studies on this topic. For this reason, the aim of this study was to validate and adapt Chemotherapy-induced Alopecia Distress Scale within the Italian context (I-CADS). Specifically, the following validations were assessed: cultural-linguistic, qualitative and quantitative content validity, psychometrics and internal consistency (reliability) assessments. To answer to the specific aims, the study design was multiphase: 1) firstly, authors provided a linguistic and cultural validation; 2) then a panel of expert (n=16) was involved to assess qualitative and quantitative content validity, using CVR, I-CVIs, S-CVI; finally 3) a cross-sectional sampling was used to establish the psychometric proprieties and the internal consistency. In the third phase the data were analyzed through different exploratory factorial analysis models, using Maximum Likelihood Robust estimator and Geomin factor rotation. I-CADS has 16 items, measuring three domains, which are self-perception, emotivism and social engaging. The items internal consistency (α Cronbach was always major of 0.93) within their domain shows a good reliability. I-CADS could be routinely used to support clinical decision-making, due to it is useful to intercept distress related to low self-perception, emotivism and social engaging. Moreover, I-CAD clear psychometric structure could facilitate its usefulness in those researches where it is needed to measure distress amongst breast cancer patients with chemotherapy-induced alopecia.

Patient-reported outcome assessment and objective evaluation of chemotherapy-induced alopecia.

PURPOSE: Alopecia is one of the most distressing side effects of chemotherapy. Evaluating and comparing the efficacy of potential therapies to prevent chemotherapy-induced alopecia (CIA) has been complicated by the lack of a standardized measurement for hair loss. In this study we investigated the correlation between patient-reported outcome assessments and quantitative measurement with the hair check to assess CIA in clinical practice. METHOD: Scalp cooling efficacy was evaluated by patients by World Health Organisation (WHO) of CIA, Visual Analogue Scale (VAS) and wig use. The Hair Check was used to determine the amount of hair (in mm2) per unit of scalp skin area (in cm2) (Hair Mass Index, HMI). CIA was also evaluated by doctors, nurses and hairdressers. RESULTS: Baseline HMI was not predictive for hair loss. HMI declined throughout all chemotherapy cycles, which was not reflected by patient-reported measures. HMI correlated with patient-reported hair quantity before the start of the therapy, but not with WHO and/or VAS during therapy. Patient's opinion correlated moderately with the opinion of doctors and nurses (ρ = 0.50-0.56 respectively), but strongly with hair dressers (ρ = 0.70). CONCLUSIONS: The Hair check is suitable to quantify the amount of hair loss and could complement research on refining outcome of scalp cooling, but the patient's opinion should be considered as the best method to assess hair loss in clinical practice. TRIAL REGISTRATION: Trialregister.nl NTR number 3082.

Cost-effectiveness analysis of scalp cooling to reduce chemotherapy-induced alopecia.

BACKGROUND: Alopecia is a frequently occurring side effect of chemotherapy that often can be prevented by cooling the scalp during the infusion. This study compared effects and costs of scalp cooling with usual general oncological care, i.e. purchasing a wig or head cover. MATERIAL AND METHODS: Scalp-cooled patients (n = 160) were compared with non-scalp-cooled patients (n = 86) at 15 Dutch hospitals. Patients were enrolled prior to anthracycline and/or taxane-based chemotherapy for several types of cancer between 2007 and 2008. Cost-effectiveness of scalp cooling compared with that of usual care was determined by the ratio of costs to quality adjusted life years (QALYs). Costs for scalp cooling (machines and nursing time), hair dressers, wigs and head covers were estimated from a societal perspective. QALYs were measured using the Short Form-36. RESULTS: Scalp cooling reduced the use of a wig or head cover by 40%, but wigs were still purchased unnecessarily by 38% of scalp-cooled patients. Average societal costs decreased therefore only by €269 per patient due to scalp cooling (p = 0.02). Given the eligibility for scalp cooling at the time, the insignificant difference in QALYs resulted from a balance of the benefits for those patients with successful scalp cooling and those without success. For the Dutch, given the generally accepted threshold of willingness to pay for a QALY (between €20 000 and €40 000), scalp cooling was cost-effective, therefore justifying the choice of scalp cooling or purchasing a wig or head cover. CONCLUSION: Given the right indication, cost-effectiveness might be improved further by postponing wig and head cover purchases, by improving scalp cooling efficacy, as well as using the scalp cooling capacity more intensively.

Comparative assessment of skin and subcutaneous toxicity in patients of advanced colorectal carcinoma treated with different schedules of FOLFOX.

OBJECTIVE: The study was designed to assess the skin and subcutaneous toxicity in patients with advanced colorectal carcinoma treated with four different schedules of FOLFOX. METHODS: The patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study as per specified inclusion criteria. Toxicity was graded according to CTC v2.0. The frequency of grade 3 and 4 adverse effects were comparatively assessed in each treatment arm. RESULTS: Very severe toxicity was attributed to the FOLFOX7 schedule. The difference between the incidence rate of grade 4 toxicity with all other grades for all parameters of skin and subcutaneous toxicity was highly significant (p=0.00<0.001). Grade 4 hand and foot syndrome was reported only in the FOLFOX7 treatment arm. The most frequent adverse symptom of skin and subcutaneous toxicity reported in the patients treated with modified schedule of FOLFOX was pruritus (grade 1). Frequency and onset of skin and subcutaneous toxic symptoms like alopecia (p=0.000), nail discoloration (p=0.021) and pruritis (p=0.000) was significantly different in each FOLFOX treatment arm. A few cases of oncholysis were also reported in the FOLFOX7 treatment arm. Hand and foot syndrome was fast progressing in patients with grade 1 toxicity. CONCLUSION: Higher frequency and severity of hand and foot syndrome and pruritus wasa found in the FOLFOX7 treatment arm. Skin and subcutaneous toxicity was comparatively low in the FOLFOX6 treatment arm.

Quantitative assessment of appearance changes and related distress in cancer patients.

OBJECTIVES: This study examined both the frequency of appearance-related symptoms and distress resulting from these symptoms in cancer patients receiving chemotherapy. METHODS: Self-report questionnaires were distributed to 753 outpatients receiving ≧ 4 weeks of treatment at an outpatient chemotherapy center. Valid responses were returned by 638 patients (response rate, 84.7%). Participants were questioned about 57 appearance-related symptoms (AS) and 23 non-appearance-related physical symptoms (non-AS); psychological well-being was assessed using a shortened version of the Derriford Appearance Scale 59. RESULTS: Questionnaire responses were obtained from 264 male and 374 female patients (mean age, 59.5 years; range, 18-85 years). Most respondents (80.3%) were concerned with changes in appearance resulting from treatment. By sex and disease type, women suffered more than men, and treatment for breast cancer created the greatest distress for women. CONCLUSION: Cancer patients are concerned about a variety of AS, and these may result in greater distress than non-AS. AS-related information and care are increasingly being sought in advance of treatment.

High-dose cyclophosphamide compared with antithymocyte globulin for treatment of acquired severe aplastic anemia.

A modified regimen of high-dose cyclophosphamide (CTX) plus cyclosporine (CsA) was adopted for patients with severe or very severe aplastic anemia, and the effectiveness was compared with a regimen of antithymocyte globulin (ATG) plus CsA. A total of 121 patients enrolled in this study received either CTX plus CsA (CTX group, 48 cases) or ATG plus CsA (ATG group, 73 cases). The early death rate was 4.2% in the CTX group and 8.2% in the ATG group, showing no significant difference (p = 0.312). The total response rate in the CTX and ATG groups was 54.2% and 57.5% at 3 months, 64.6% and 72.6% at 6 months, and 72.9% and 78.1% at 12 months, respectively (p > 0.05). The overall 5-year survival rate was 81.2% and 80.7%, and the event-free survival rate was 68.2% and 67.3% in the CTX and ATG groups, respectively (p > 0.05). The total medical cost of the CTX group was 54.8% less than that of ATG regimen (p = 0.000). In summary, treatment of severe or very severe aplastic anemia with CTX plus CsA has effectiveness that is comparable to a conventional regimen and less costly.

[Safety analysis of ambulatory chemotherapy in lung cancer].

BACKGROUND AND OBJECTIVE: Ambulatory chemotherapy has now been a popular way of treatment in developed countries, for its less medical costs and incidence of adverse events. The aim of this study is to estimate the feasibility and safety of ambulatory chemotherapy in lung cancer in Shanghai chest hospital. METHODS: Medical data including performance status, cycles of chemotherapy, pathologic type, adverse events in hospital and adverse events after discharge from hospital. RESULTS: We estimated a total of 1 573 lung cancer patients admitted in Shanghai chest hospital, during October 2008 to April 2009, including 416 patients treated in the way of ambulatory chemotherapy, 1 157 patients treated in the routine way. Rate of grade III/IV gastrointestinal toxicity was fewer in the ambulatory chemotherapy group (21.88%) than routine chemotherapy group (P < 0.01); meanwhile, rate of leukopenia was higher in the ambulatory chemotherapy group (49.28%) than routine chemotherapy group (35.0%)(P < 0.01). Days of hospitalization and medical costs were less in the ambulatory chemotherapy group (4.48 d vs 14.04 d, 6 911.32 vs 14 623.59, all P < 0.01). CONCLUSIONS: Ambulatory chemotherapy is a favorable way to promote.

The impact of cancer and chemotherapy: perceptual similarities and differences between cancer patients, nurses and physicians.

BACKGROUND: An essential condition to provide optimal care to cancer patients is a thorough understanding of the worries and needs of these patients. PURPOSE: To assess and compare perceptions about the impact of cancer and chemotherapy of health-care providers and patients. METHODS: Breast cancer survivors (N=80), oncology nurses (N=41) and physicians (N=49) with oncology experience completed a psychophysical scaling method with items tapping both the physical and psychosocial effects of cancer and chemotherapy. RESULTS: The following five issues ranked highest among patients: fear of metastases, fatigue, consciousness of one's own vulnerability, hair loss and nausea. Whereas there was a strong correspondence between the ratings of nurses and physicians, both groups grossly overestimated and underestimated various issues. For example, the effects on relationships with partners and children were greatly overestimated by nurses, while physicians underestimated hair loss the most. CONCLUSIONS: There was a considerable discrepancy on various issues between perceptions of patients and medical professionals. CLINICAL IMPLICATION: The observed lack of correspondence between patients and health-care providers may result in inappropriate provision of attention and health care. Methods have to be developed to assess easily the main needs and worries of individual patients, which is an essential condition to be able to provide optimal care.

Using nursing diagnoses in prevention and management of chemotherapy-induced alopecia in the cancer patient.

PURPOSE: To explore the use of NANDA, NIC, and NOC classification systems in the psychological and physical care of patients experiencing chemotherapy-induced alopecia. METHOD: Review of the literature on alopecia in relation to the NANDA nursing diagnosis classification. FINDINGS: Two key nursing diagnoses are related to alopecia. One is disturbed body image and the other is grieving. CONCLUSION: By using nursing diagnoses, the nurse can identify the defining characteristics associated with the specific problems experienced by the patient with alopecia. PRACTICE IMPLICATIONS: Moving from the nursing diagnoses, the nurse can develop individualized nursing interventions and generate a realistic outcome in collaboration with the patient.

Postmenopausal women with breast cancer: their experiences of the chemotherapy treatment period.

This article illustrates the experience of 20 postmenopausal women with breast cancer who had received chemotherapy treatment. The interviews were of narrative nature and analyzed with content analysis. Four themes, including 12 subthemes, described these women's life during treatment as a journey from the negative experiences of fear of the unknown, affects on body and mind, to the more positive to get by, and a transformed life. The treatment was compared with an assault on the body, and the loss of their hair was experienced more negatively than the loss of a breast. The women described a feeling of imbalance in their relationships due to lack of support from those close to them. The support from healthcare professionals was experienced both positively and negatively, and many of the women revealed variation in the professional's attitude, knowledge, and empathy. The women who chose not to work during the treatment felt pressure from society and healthcare professionals to get back to work as soon as possible. For many, especially those in a leading position, this was experienced as very difficult. The women expressed a feeling of not being afraid of dying but wanted more time to prepare themselves.

Combination of docetaxel, estramustine phosphate, and zoledronic acid in androgen-independent metastatic prostate cancer: efficacy, safety, and clinical benefit assessment.

OBJECTIVES: Docetaxel is an effective agent for the treatment of androgen-independent prostate cancer (AIPC). Its combination with estramustine phosphate (EMP) has shown promising results in AIPC but the toxicity remains considerable. In an effort to minimize toxicity, we designed an every-2-week docetaxel administration regimen with a 3-day low-dose EMP regimen. Patients with bone metastases also received zoledronic acid. METHODS: A total of 54 patients with AIPC received docetaxel at 45 mg/m2 and EMP (140 mg orally every 8 hours for nine doses) every 2 weeks. Zoledronic acid was administered at 4 mg every 28 days. RESULTS: Of the 49 assessable patients, 22 (45%, 95% confidence interval [CI] 31% to 60%) had a prostate-specific antigen response. Of 24 patients with measurable disease, 9 (38%, 95% CI 19% to 59%) had a response to therapy (one complete response and eight partial responses). The median time to progression was 4.4 months (95% CI 2.7 to 6), and overall survival was 13.3 months (95% CI 9 to 17.6). Toxicity was mild, with only 5 cases of grade 3 or 4 toxicity. The pain score improved by 1 point in 21 (54%) of 39 symptomatic patients, and 14 (40%) of 38 patients who used analgesics discontinued analgesic consumption by the end of treatment. CONCLUSIONS: The combination of an every-2-week regimen of docetaxel, EMP, and zoledronic acid is an effective, well-tolerated regimen that results in symptomatic improvement in a significant proportion of patients with AIPC.