Topical interventions for preventing hand-foot syndrome resulting from antineoplastic therapy: A scoping review / Intervenciones tópicas para prevenir el síndrome mano-pie resultante de la terapia antineoplásica: revisión del alcance / Intervenções tópicas para prevenção de síndrome mão-pé decorrente de terapia antineoplásica: revisão de escopo

ABSTRACT Objective: To map topical interventions used to prevent hand-foot syndrome in cancer patients undergoing antineoplastic therapy. Method: This is a scoping review reported in accordance with the recommendations of PRISMA-ScR (extension for scoping review) and the Joanna Briggs Institute Manual. The searches were carried out in the electronic databases CINAHL, Cochrane CENTRAL, EMBASE, LILACS, LIVIVO, PubMed, Scopus, Web of Science; and gray literature (Google Scholar, Pro-Quest). Results: The searches resulted in 12,016 references and the final sample consisted of 45 studies. A total of 42 topical interventions were identified, including: moisturizing creams, corticosteroids, acids, mapisal, silymarin, and henna. However, urea was the most cited intervention (62%). As for the presentations of the interventions, they varied among creams, ointments, gels, hydrocolloids, decoctions, patches, powders, oils, and soaps. Conclusion: The results allowed reviewing topical interventions, with emphasis on the use of urea and moisturizing creams. However, most of the interventions identified in this review require evaluation in future studies for better understanding of their benefits.

RESUMEN Objetivo: Mapear las intervenciones tópicas utilizadas para prevenir el síndrome mano-pie en pacientes con cáncer sometidos a terapia antineoplásica. Método: Esta es una revisión del alcance reportada de acuerdo con las recomendaciones de PRISMA-ScR (extensión para la revisión del alcance) y el Manual del Instituto Joanna Briggs. Las búsquedas se realizaron en las bases de datos electrónicas CINAHL, Cochrane CENTRAL, EMBASE, LILACS, LIVIVO, PubMed, Scopus, Web of Science; y literatura gris (Google Scholar, Pro-Quest). Resultados: Las búsquedas resultaron en 12.016 referencias y la muestra final estuvo compuesta por 45 estudios. Se identificaron 42 intervenciones tópicas, entre ellas: cremas humectantes, corticoides, ácidos, mapisal, silimarina y henna. Sin embargo, la urea fue la intervención más citada (62%). En cuanto a las presentaciones de las intervenciones, variaron entre cremas, ungüentos, geles, hidrocoloides, decocciones, parches, polvos, aceites y jabones. Conclusión: Los resultados permitieron revisar las intervenciones tópicas, con énfasis en el uso de urea y cremas humectantes. Sin embargo, la mayoría de las intervenciones identificadas en esta revisión deben evaluarse en estudios futuros para mejor comprensión de sus beneficios.

RESUMO Objetivo: Mapear as intervenções tópicas utilizadas para a prevenção da síndrome mão-pé em pacientes com câncer em terapia antineoplásica. Método: Trata-se de uma revisão de escopo reportada de acordo com as recomendações do PRISMA-ScR (extensão para revisão de escopo) e o Manual do Instituto Joanna Briggs. As buscas foram realizadas nas bases eletrônicas CINAHL, Cochrane CENTRAL, EMBASE, LILACS, LIVIVO, PubMed, Scopus, Web of Science; e literatura cinzenta (Google Scholar, Pro-Quest). Resultados: As buscas resultaram em 12.016 referências e a amostra final foi composta por 45 estudos. Um total de 42 intervenções tópicas foram identificadas, dentre elas: cremes hidratantes, corticosteroides, ácidos, mapisal, silimarina e henna. Entretanto, a ureia foi a intervenção mais citada (62%). Quanto às apresentações das intervenções, estas variaram entre cremes, pomadas, géis, hidrocoloides, decocções, adesivos, pós, óleos e sabões. Conclusão: Os resultados possibilitaram uma recensão das intervenções tópicas, com destaque ao uso da ureia e cremes hidratantes. Todavia, grande parte das intervenções identificadas nesta revisão necessitam ser avaliadas, em estudos futuros, para melhor compreensão dos seus benefícios.

Predictive Power of Demographic and Clinicopathological Aspects of Patients with Acral Melanoma: a Single-Center Series Of 394 Cases in Brazil / Poder Preditivo dos Aspectos Demográficos e Clinicopatológicos de Pacientes com Melanoma Acral: uma Série de 394 Casos em um Único Centro no Brasil / Poder Predictivo de Aspectos Demográficos y Clinicopatológicos en Pacientes con Melanoma Acral: una Serie de 394 Casos en un Solo Centro en el Brasil

Introduction: Acral melanoma (AM) is associated with high mortality and poor survival, and its prognosis is worse compared to other melanoma subtypes. Objective: To analyze the predictive power of demographic and clinicopathological aspects in patients with AM. Method: This is a retrospective study with patients diagnosed with AM between January 2001 and December 2015. Demographic and clinicopathological characteristics were collected. The outcome was 5-year overall survival (OS). Kaplan-Meier curves, log rank-test and Cox regression analysis were used. Results: The study identified 394 patients with AM. The 5-year survival rate for patients with AM was found to be 45.6%. The predictive factors of OS included Breslow thickness [hazard ratio (HR): 1.02, 95% confidence interval (CI): 1.01-1.03], ulceration (HR: 4.06, 95%CI: 2.18-7.57) and lymphovascular invasion (LVI) (HR: 2.12, 95%CI:1.12-4.00). Conclusion: The findings highlight the poor prognosis of AM and the predictive power of Breslow thickness, ulceration and LVI

Introdução: O melanoma acral (MA) está associado à alta mortalidade e à baixa sobrevida, e seu prognóstico é pior em comparação com os outros subtipos de melanoma. Objetivo: Analisar o poder preditivo de aspectos demográficos e clinicopatológicos em pacientes com MA. Método: Estudo retrospectivo com pacientes diagnosticados com MA entre janeiro de 2001 e dezembro de 2015. Foram coletadas características demográficas e clinicopatológicas. O desfecho foi a sobrevida global (SG) em cinco anos. Foram utilizados curvas de Kaplan-Meier, teste de log-rank e análise de regressão de Cox. Resultados: Foram identificados 394 pacientes com MA. A taxa de sobrevida em cinco anos para pacientes com MA foi de 45,6%. Os fatores preditivos da SG incluíram espessura de Breslow [hazard ratio (HR): 1,02, intervalo de confiança (IC) de 95%: 1,01-1,03], ulceração (HR: 4,06, IC 95%: 2,18-7,57) e invasão linfovascular (ILV) (HR: 2,12, IC 95%: 1,12-4,00). Conclusão: Tais achados destacam o prognóstico desfavorável do MA e o poder preditivo da espessura de Breslow, ulceração e ILV

Introducción: El melanoma acral (MA) está asociado con una alta mortalidad y una baja supervivencia, y su pronóstico es peor en comparación con los otros subtipos de melanoma. Objetivo: Analizar el poder predictivo de los aspectos demográficos y clinicopatológicos en pacientes con MA. Método: Estudio retrospectivo con pacientes diagnosticados con MA entre enero de 2001 y diciembre de 2015. Se recopilaron características demográficas y clinicopatológicas. El resultado fue la supervivencia global (SG) a los cinco años. Se utilizaron curvas de Kaplan-Meier, prueba de log-rank y análisis de regresión de Cox. Resultados: Se identificaron 394 pacientes con MA. La tasa de supervivencia a cinco años para los pacientes con MA fue del 45.6%. Los factores predictivos de la SG incluyeron el grosor de Breslow [razón de peligro (HR): 1.02, intervalo de confianza del 95% (IC): 1.01-1.03], la ulceración (HR: 4.06, IC del 95%: 2.18-7.57) y la invasión linfovascular (ILV) (HR: 2.12, IC del 95%: 1.12-4.00). Conclusión: Estos hallazgos resaltan el pronóstico desfavorable del MA y el poder predictivo del grosor de Breslow, la ulceración y la ILV

Diagnóstico de espondiloartrite axial em pacientes com fibromialgia / Axial spondyloarthritis diagnosis in fibromyalgia patients

Objetivo: Avaliar pacientes com fibromialgia e dor lombar, bus- cando características clínicas de espondiloatrites axiais. Méto- dos: Neste estudo transversal, cem pacientes com fibromialgia e idades entre 18 e 65 anos foram avaliados. A avaliação consis- tiu em um questionário baseado no braço clínico dos critérios Assessment of Spondyloarthritis International Society para diag- nóstico de espondiloatrites axiais e um questionário de impacto da fibromialgia (Revised Fibromyalgia Impact Questionnaire). Re- sultados: Quando o braço clínico da Assessment of Spondyloar- thritis International Society foi aplicado em pacientes com fibro- mialgia e dor lombar, 80% dos pacientes preencheram os critérios para diagnóstico de espondiloatrites axiais. As principais carac- terísticas de espondiloatrite axial foram dor lombar inflamatória, boa resposta a drogas anti-inflmatórias não esteroidais, artrite e entesite. Pacientes com critérios de espondiloatrites axiais posi- tivos apresentaram maiores níveis séricos de proteína C-reativa (p=0,00035). O valor médio do Revised Fibromyalgia Impact Ques- tionnaire para todos os pacientes avaliados foi 63,6, e não houve di- ferença entre os pacientes que preencheram os critérios e aqueles que não preencheram. Conclusão: Pacientes com fibromialgia e dor lombar frequentemente apresentam características clínicas de espondiloatrite axial, e aqueles que preencheram os crité- rios clínicos para espondiloatrites axiais também apresentaram maiores níveis séricos de proteína C-reativa.

Objective: To evaluate patients with fibromyalgia and back pain for clinical features of axial spondyloarthritis. Methods: In this cross-sectional study, one hundred fibromyalgia patients between 18 and 65 years old were assessed. The assessment consisted of a questionnaire based on the clinical arm ofthe Assessment of Spondyloarthritis International Society criteria for the diagnosis of axial spondyloarthritis and a questionnaire on the impact of fibromyalgia (Revised Fibromyalgia Impact Questionnaire). Re- sults: When the clinical arm of the Assessment of Spondyloarthri- tis International Society was applied in patients with fibromyal- gia and back pain, 80% of the patients met the clinical criteria for diagnosis of axial spondyloarthritis. The main features of axial spondyloarthritis in fibromyalgia patients were inflammatory back pain, good response to non-steroidal anti-inflammatory drugs (NSAIDs), arthritis, and enthesitis. Patients with positive axial spondyloarthritis criteria presented with higher C- reac- tive protein levels (p=0.00035). The mean value of the Revised Fibromyalgia Impact Questionnaire for all patients assessed was 63.6 and there was no difference between patients that met the criteria for axial spondyloarthritis and those who did not. Con- clusion: Patients with fibromyalgia and back pain often present clinical features of axial spondyloarthritis, and those who met the clinical criteria for axial spondyloarthritis also presented with higher levels of C-reactive protein.

Clinical response and safety of apatinib monotherapy in recurrent, metastatic cervical cancer after failure of chemotherapy: a retrospective study / 부인종양

Real world effectiveness and safety of pegylated liposomal doxorubicin in platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer: a Korean multicenter retrospective cohort study / 부인종양

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533

Chinese expert consensus on management of adverse events of pegylated liposomal doxorubicin (2020 edition) / 中华肿瘤杂志

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.

Effect of ozone oil for prevention and treatment of sorafenib-induced hand-foot skin reactions: a randomized controlled trial / 南方医科大学学报

OBJECTIVE@#To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC).@*METHODS@#A total of 99 patients diagnosed with advanced HCC according to National Comprehensive Cancer Network (NCCN) who were scheduled to receive sorafenib treatment for the first time were enrolled in this study between April, 2018 and January, 2020. The patients were randomized into medical ozone oil group (@*RESULTS@#Eight patients were excluded for poor compliance or protocol violations, leaving a total of 91 patients for analysis, including 44 in medical ozone oil group and 47 in urea ointment group. Sixteen (36.4%) of patients in ozone oil group developed HFSR, a rate significantly lower than that in urea ointment group (57.4%; @*CONCLUSIONS@#Medical ozone oil can significantly reduce the incidence and severity of HFSR to improve the quality of life of HCC patients receiving sorafenib treatment.

Síndrome Mão-Pé Induzida por Quimioterapia: Abordagem Clínica e Epidemiológica de Pacientes com Câncer / Chemotherapy-Induced Hand-Foot Syndrome: Clinical and Epidemiological Approach to Cancer Patients / Síndrome Mano-Pie Inducida por Quimioterapia: Enfoque Cínico y Epidemiológico de Pacientes con Cáncer

Introdução: A síndrome mão-pé (SMP) ou eritrodisestesia palmopalmar é uma reação cutânea tóxica decorrente da quimioterapia antineoplásica, que ocorre com frequência e constitui importante problema clínico ao indivíduo com neoplasia maligna. O desenvolvimento da SMP pode levar à interrupção do tratamento e, com frequência, à redução da dose do quimioterápico. Objetivo: Analisar os dados clínicos e epidemiológicos de pacientes com SMP tratados com quimioterapia. Método: Estudo descritivo e retrospectivo, com coleta de dados realizada entre janeiro de 2013 e janeiro de 2014 em prontuários utilizando-se do registro de toxicidades dos antineoplásicos e da Escala de Performance Status do Eastern Cooperative Oncology Group. Resultados: Foram analisados 250 prontuários. Destes, 70 realizaram tratamento quimioterápicos e 15 (21,4%) apresentaram SMP, com toxicidade grau 1 após uso de dois ciclos de capecitabina (13,3%); grau 2 após dois, quatro e até 12 ciclos de tratamento (40%); grau 3 após cinco e 11 ciclos de capecitabina (20%); e, em grau 4, um paciente apresentou toxicidade após dois ciclos de capecitabina e outro, apresentou SMP após dois ciclos de doxorrubicina lipossomal (13,3%). Conclusão: O tratamento com quimioterapia causa alto risco de apresentar SMP. No entanto, mostrou baixa incidência dessa síndrome em pacientes com câncer que fazem tratamento com capecitabina, doxorrubicina e citarabina.

Introduction:Hand-foot syndrome (HFS) or palmar-plantar erythrodysesthesia is a toxic skin reaction resulting from antineoplastic chemotherapy, which occurs frequently and is an important clinical problem for individuals with malignant neoplasm. The development of HFS may lead to treatment discontinuation and, often, a reduction of the chemotherapy dose. Objective: To analyze the clinical and epidemiological data of patients with HFS treated with chemotherapy. Method: A descriptive and retrospective study, with data collected from January 2013 to January 2014 in medical charts using the register of antineoplastic toxicities and the Eastern Cooperative Oncology Group Performance Status scale. Results: It were analyzed 250 charts. Of these, 70 underwent chemotherapy treatment, and 15 (21.4%) presented HFS, with grade 1 toxicity after 2 cycles of capecitabine (13.3%); grade 2 after two, four and up to 12 treatment cycles (40%); grade 3, after five and 11 cycles of capecitabine (20%) and with grade 4, one patient presented such toxicity after two cycles of capecitabine and another patient presented HFS after two cycles of liposomal doxorubicin (13.3%). Conclusion: Chemotherapy treatment causes high risk of presenting HFS. However, this syndrome showed low incidence in cancer patients receiving treatment with capecitabine, doxorubicin and cytarabine.

Introducción: El síndrome de manos y pies (SMP) o la eritrodistesia palmopalmar es una reacción cutánea tóxica resultante de la quimioterapia antineoplásica, que ocurre con frecuencia y es un problema clínico importante para las personas con neoplasia maligna. El desarrollo del SMP puede conducir a la interrupción del tratamiento y, a menudo, a una reducción de la dosis de quimioterapia. Objetivo: Analizar los datos clínicos y epidemiológicos de pacientes con SPM tratados con quimioterapia. Método:Estudio descriptivo y retrospectivo, con recopilación de datos realizada entre enero de 2013 y enero de 2014 en registros médicos utilizando el registro de toxicidad antineoplásica y la Escala de estado de rendimiento del Grupo de Oncología Cooperativa del Este. Resultados: Se analizaron 250 registros médicos. De estos, 70 se sometieron a tratamiento de quimioterapia y 15 (21,4%) presentaron SMP. Con toxicidad de grado 1 después del uso de 2 ciclos de capecitabina (13,3%); grado 2 después de dos, cuatro y hasta doce ciclos de tratamiento (40%); grado 3 después de cinco y 11 ciclos de capecitabina (20%); grado 4, y un paciente presentó dicha toxicidad después de dos ciclos de capecitabina y otro paciente presentó SMP después de dos ciclos de doxorrubicina liposomal (13,3%). Conclusión: El tratamiento con quimioterapia causa un alto riesgo de presentar SMP. Sin embargo, ha mostrado una baja incidencia de este síndrome en pacientes con cáncer que reciben capecitabina, doxorrubicina y citarabina.

Identificação, Prevenção e Tratamento da Síndrome Mão-Pé Induzida por Quimioterapia: Revisão Sistemática / Identification, Prevention and Treatment of Hand-Foot Syndrome Induced by Chemotherapy: Systematic Review / Identificación, Prevención y Tratamiento de la Enfermedad Mental por Quimioterapia: Revisión Sistemática

Introdução: A síndrome mão-pé é uma reação adversa experimentada por vários pacientes em tratamento para o câncer e fator preditor de morbidade e mortalidade. Objetivo: Avaliar as evidências científicas relacionadas à identificação, prevenção e tratamento da síndrome mão-pé induzida por agentes quimioterápicos, identificar os principais sinais e sintomas que possibilitam o reconhecimento da síndrome e, ainda, discutir a ocorrência de onicomicoses no contexto da síndrome mão-pé. Método: Trata-se de uma revisão sistemática na MEDLINE/PubMed, Biblioteca Virtual da Saúde e Scopus, incluindo literatura cinzenta e busca manual. Os 29 estudos incluídos na revisão foram analisados e classificados segundo a hierarquia dos níveis de evidência Grading of Recommendations Assessment, Development and Evaluations (GRADE) e a confiabilidade entre os examinadores (coeficiente Kappa) foi calculada. Resultados: Foram identificados estudos que demonstraram eficácia na prevenção da síndrome mão-pé com o uso da crioterapia e hidroterapia. Evidenciaram-se resultados satisfatórios com o uso do creme de ureia na prevenção e tratamento, e o uso de piridoxina não apresentou resultados conclusivos. Foram encontrados mecanismos para identificação da síndrome e para classificação dos agentes indutores. O grupo dos taxanos predominou entre os medicamentos indutores da síndrome mão-pé. Conclusão: Existem evidências consistentes, porém não contemplam todos os fármacos indutores da síndrome e não exploram outras manifestações relacionadas às onicólises e onicomicoses. O estudo apresentou resultados que poderão auxiliar os prescritores na identificação da síndrome mão-pé, além de alternativas para prevenção e tratamento. Contudo, vale destacar a necessidade de pesquisas futuras para elucidar a etiologia e protocolos de tratamento.

Introduction: Hand-foot syndrome is an adverse reaction experienced by many cancer patients and a predictor of morbidity and mortality. Objective:To evaluate the scientific evidence related to the identification, prevention and treatment of chemotherapeutic-induced hand-foot syndrome, to identify the main signs and symptoms that enable the recognition of the syndrome, and to discuss the occurrence of onychomycosis in the context of the hand-foot syndrome. Method: This is a systematic review at MEDLINE/PubMed, Virtual Health Library and Scopus, including gray literature and manual search. The 29 studies included in the review were analyzed and graded according to the hierarchy of evidence levels Grading of Recommendations Assessment, Development and Evaluations (GRADE) and reliability among examiners (Kappa coefficient) was calculated. Results:It were identified studies that demonstrated efficacy in preventing hand-foot syndrome using cryotherapy and hydrotherapy. Satisfactory results were evidenced with the use of urea cream for prevention and treatment, and the use of pyridoxine showed inconclusive results. Mechanisms for identification of the syndrome and classification of inducing agents were found. The taxane group predominated among hand-foot syndrome inducing drugs. Conclusion: There are consistent evidences but do not include all drugs inducing the syndrome and do not explore other manifestations related to onycholysis and onychomycosis. The study presented results that may help prescribers to identify hand-foot syndrome, as well as alternatives for prevention and treatment. However, it is worth highlighting the need for future studies to elucidate the etiology and treatment protocols.

Introducción: El síndrome de pies y manos es una reacción adversa experimentada por muchos pacientes con cáncer y un predictor de morbilidad y mortalidad. Objetivo: Evaluar la evidencia científica relacionada con la identificación, prevención y tratamiento del síndrome de pies y manos inducido por quimioterapia, identificar los principales signos y síntomas que permiten el reconocimiento del síndrome y analizar la aparición de onicomicosis en el contexto del síndrome mano-pie. Método:Esta es una revisión sistemática en MEDLINE/PubMed, Virtual Health Library y Scopus, que incluye literatura gris y búsqueda manual. Los 29 estudios incluidos en la revisión se analizaron y clasificaron de acuerdo con la jerarquía de los niveles de evidencia Grading of Recommendations Assessment, Development and Evaluations (GRADE). Resultados: Identificamos estudios que demostraron eficacia en la prevención del síndrome mano-pie usando crioterapia e hidroterapia. También mostraron resultados satisfactorios con el uso de crema de urea en la prevención y el tratamiento, y el uso de piridoxina no mostró resultados concluyentes. Se encontraron mecanismos para la identificación del síndrome y la clasificación de los agentes inductores. El grupo de taxanos predominó entre los fármacos inductores del síndrome mano-pie. Conclusión: Existe evidencia consistente pero no incluye todas las drogas que inducen el síndrome y no explora otras manifestaciones relacionadas con la onicólisis y la onicomicosis. El estudio presentó resultados que pueden ayudar a los prescriptores a identificar el síndrome de manos y pies, así como alternativas para la prevención y el tratamiento. Sin embargo, vale la pena destacar la necesidad de futuras investigaciones para dilucidar la etiología y los protocolos de tratamiento.

S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS. RESULTS: There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs. 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea. CONCLUSION: Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

Hand-foot syndrome due to hepatitis C therapy

SUMMARY INTRODUCTION Direct-acting antivirals are new drugs for chronic hepatitis C treatment. They are usually safe and well tolerated, but can sometimes cause serious adverse effects and there is no consensus on how to treat or prevent them. We described a case of hand-foot syndrome due to hepatitis C virus interferon-free therapy. METHODS We report the case of a 49-year-old man with compensated liver cirrhosis due to chronic hepatitis C genotype 1, treatment-naïve, who started viral treatment with sofosbuvir, simeprevir and ribavirin for 12 weeks. RESULTS At the sixth week of treatment he had anemia, requiring a lower dose of ribavirin. At the tenth week, he had erythematous, pruritic, scaly and flaky lesions on hands and feet, which showed a partial response to oral antihistamines and topical corticosteroids. It was not necessary to discontinue antiviral treatment, but in the first week after the end of treatment, there was worsening of injuries, including signs of secondary infection, that required hospitalization, antibiotics and oral corticosteroid, with progressive improvement. Biopsy of the lesions was consistent with pharmacodermia. The patient had sustained a virological response, despite the side effect. He had a history of pharmacodermia one year ago attributed to the use of topiramate, responsive to oral corticosteroid. CONCLUSION Interferon-free therapies can rarely lead to severe adverse reactions, such as skin lesions. Patients receiving ribavirin combinations and those who had a history of pharmacodermia or skin disease may be more susceptible. There is no consensus on how to prevent skin reactions in these patients.

RESUMO INTRODUÇÃO Antivirais de ação direta são as novas drogas utilizadas no tratamento da hepatite C crônica. São geralmente seguros, com boa tolerância, mas eventualmente podem causar efeitos adversos graves, e não há consenso sobre como tratá-los ou preveni-los. Descrevemos um caso de síndrome mão-pé secundária à terapia livre de interferon para hepatite C crônica. Materiais e métodos Relatamos o caso de um paciente de 49 anos com cirrose hepática compensada secundária à hepatite C crônica, genótipo 1, virgem de tratamento, que iniciou terapia com sofosbuvir, simeprevir e ribavirina por 12 semanas. Resultados Na sexta semana de tratamento, apresentou anemia, sendo necessária redução de dose da ribavirina. Na 20a semana, apresentou lesões eritematosas e descamativas, com prurido em mãos e pés, que teve resposta parcial ao uso de anti-histamínico oral e corticoide tópico. Não foi necessário descontinuar os antivirais, mas na primeira semana após o término do tratamento, houve piora das lesões, com sinais de infecção secundária, sendo necessárias hospitalização e terapia com antibiótico e corticoide oral, com melhora progressiva. Biópsias das lesões foram compatíveis com farmacodermia. O paciente teve resposta virológica sustentada, apesar dos efeitos adversos. Tinha história de farmacodermia há um ano, atribuída ao uso de topiramato, responsiva a corticoterapia oral. Conclusão Os tratamentos livres de interferon raramente causam eventos adversos graves, como lesões cutâneas. Pacientes em uso de ribavirina e com história de farmacodermia ou doença cutânea prévia podem ser mais susceptíveis. Não existe consenso sobre como prevenir reações cutâneas nesses pacientes.

Síndrome mão-pé induzida por capecitabina: relato de caso / Capecitabine-induced hand-foot syndrome: a case repor / Síndrome mano-pie inducido por capecitabina: relato de caso

A capecitabina é um agente quimioterápico indicado, dentre outros casos, como monoterapia no câncer de mama metastático. A síndrome mão-pé consiste numa das reações adversas associadas ao seu uso e caracteriza-se por eritema doloroso, edema, disestesia, descamação, bolhas e úlceras nas regiões palmar e plantar. Objetivou-se descrever o caso de uma paciente portadora de carcinoma de mama esquerda com metástase hepática que apresentou síndrome mão-pé decorrente do tratamento com capecitabina. Trata-se de um relato de caso ocorrido num hospital universitário de um estado do nordeste do Brasil em 2016. Foi necessária a suspensão do protocolo antineoplásico utilizado. Observou-se remissão parcial dos sintomas após o uso do gel de Aloe vera para o tratamento das áreas afetadas. Ressalta-se a importância do relato para conhecimento dessa reação adversa, facilitando sua identificação e manejo, para promover melhora da qualidade de vida do paciente oncológico (AU).

Capecitabine is a chemotherapeutic agent indicated, among other things, as monotherapy for metastatic breast cancer. Hand-foot syndrome is one of the adverse effects associated with its use and is characterized by painful erythema, edema, dysesthesia, desquamation, blistering and ulcers in the palms and soles. This study presents a case report on a patient with left-sided breast cancer metastasized to the liver, who suffered from capecitabine-induced hand-foot syndrome. The patient was being treated at a university hospital in a state in the Northeast of Brazil in 2016. Her antineoplastic protocol had to be suspended. After the use of Aloe vera gel to treat the affected areas, there was a partial remission of symptoms.It is important to expand knowledge about this adverse reaction, facilitating its identification and management, in order to improve quality of life in cancer patients (AU).

La capecitabina es un agente quimioterápico indicado, entre otros casos, como monoterapia en cáncer de mama metastático. El síndrome mano-pie consiste en una de las reacciones adversas asociadas a su uso, caracterizada por eritema doloroso, edema, parestesia, descamación, ampollas y úlceras en regiones palmar y plantar. Se objetivó describir el caso de una paciente con carcinoma en mama izquierda, con metástasis hepática presentando síndrome de mano-pie derivado del tratamiento con capecitabina. Relato de caso ocurrido en hospital universitario de estado del Noreste brasileño en 2016. Fue necesaria la suspensión del protocolo antineoplásico utilizado. Se observó remisión parcial de los síntomas luego de uso de gel de Aloe Vera para tratamiento de las áreas afectadas. Se destaca la importancia del relato para conocimiento de esta reacción adversa, permitiendo su identificación y manejo, promoviendo mejora de calidad de vida del paciente oncológico (AU).

Do you know this syndrome? Hand-foot syndrome

ABSTRACT Hand-foot syndrome is a common cutaneous adverse effect associated with certain systemic chemotherapy drugs. It is characterized by erythema, edema, and burning sensation, especially over palmoplantar surfaces. We report the case of an elderly patient undergoing chemotherapy after a breast cancer surgery who developed symptoms two months after the start of the regimen. There are no studies that explore specific therapies. Suggestive therapy include reducing agent dosage, increasing the interval between cycles, or even stopping chemotherapy. Emollients, analgesics, and cold packs are described as effective. After alopecia and mucositis, hand-foot syndrome is the most common adverse dermatologic reaction to chemotherapeutic agents.

Analysis of Dermatologic Diseases in Patients Receiving Anticancer Treatments: A Retrospective Study of 140 Cases / 대한피부과학회지

BACKGROUND: A number of anticancer agents are known to induce many adverse reactions in the skin. Related cutaneous adverse drug reactions influence the morbidity, mortality, and anti-cancer regimen of the patients. A multidisciplinary approach to cancer management has been emphasized. OBJECTIVE: To identify the causative anticancer agents and frequency of adverse reactions in the skin. METHODS: We retrospectively reviewed the medical records of patients who consulted at the Dermatology Department of Busan Paik Hospital and Haeundae Paik Hospital from January 2013 to February 2015. RESULTS: A total of 140 patients were enrolled. Among the 45 patients treated with antimetabolite analogs (30 cytarabine, 7 gemcitabine, 3 methotrexate, 2 fludarabine, 2 doxifluridine, and 1 decitabine), exanthematous drug eruption (49.1%) was the most common reaction, followed by hand-foot syndrome (28.3%). Among the 35 patients treated with fluorouracil (22 5-fluorouracil and 13 capecitabine), hand-foot syndrome (47.2%) was the most common, followed by acneiform eruption (25.0%). Among the 24 patients treated with epidermal grow factor receptor inhibitors (10 erlotinib, 10 cetuximab, and 4 gefitinib), acneiform eruption (54.8%) was the most common, followed by xerosis (19.4%). Among the 11 patients treated with anthracyclines (9 doxorubicin, 1 daunorubicin, and 1 idarubicin), acneiform eruption (45.5%) was the most common, followed by hand-foot syndrome (36.4%). Among the 7 patients treated with taxanes (4 docetaxel and 3 paclitaxel), hand-foot syndrome (42.8%) was the most common. Among the 6 patients treated with angiogenesis-inducing inhibitors (3 sorafenib, 2 pazopanib, and 1 sunitinib), hand-foot skin reaction (66.7%) was the most common. Only 2 patients (1.4%) changed treatments due to intolerable skin reactions. CONCLUSION: Clinicians should be aware of the various skin reactions of anticancer agents and predict their clinical course effectively.

The efficacy and safety of pegylated liposomal doxorubicin monotherapy and combination therapy with carboplatin in Korean patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer: a single-institution experience

OBJECTIVE: This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) with or without carboplatin in Korean patients with recurrent ovarian cancer (ROC), fallopian tube, or primary peritoneal cancer. METHODS: This retrospective study included 52 patients with ROC, fallopian tube, or primary peritoneal cancer who received PLD (50 mg/m²) between 1(st) December 2014 and 31(th) July 2016. RESULTS: The mean number of chemotherapy cycles was 3.8 (range, 2 to 9) in the PLD monotherapy group and 7 (range, 2 to 13) in the PLD combined with carboplatin (PLD-C) group. In overall response rates and clinical beneficial rates, PLD monotherapy group shows 5.0% and 17.5%, and PLD-C group shows 33.3% and 75.0%. The mean progression-free survival (PFS) was 5 and 13 months in the PLD monotherapy and PLD-C groups, respectively. At 6 months after treatment initiation, absence of disease progression was confirmed in 6 (15%) and 10 (83.3%) patients in the PLD monotherapy and PLD-C groups. Hematological adverse events (e.g., neutropenia and thrombocytopenia) were more common in the PLD-C group (P<0.001, P=0.004). The incidence of anemia and non-hematological adverse events, including mucositis, hand-foot syndrome, and allergic reactions, was similar in both groups. CONCLUSION: This study demonstrated the efficacy and safety of PLD monotherapy and PLD-C combination in Korean patients with ROC. This study would be helpful to consider the degree of worry about side effects and treatment expectations after treatment. Further retrospective studies with larger samples are required to confirm the efficacy of PLD monotherapy in Asian patients with platinum-resistant ROC.

Eritrodisestesia o síndrome mano pie. Presentación de dos casos y revisión de la literatura / Erythrodysesthesia or foot hand syndrome Presentation of two cases and review of the literature

La eritrodisestesia, o síndrome mano pie, es una reacción adversa relacionada con algunos agentes quimioterápicos. Se caracteriza por comenzar con un pródromo de disestesia palmo-plantar y, entre 2 a 4 días, la sensación progresa a un dolor quemante con edema y eritema en placas bien delimitadas y simétricas. Los quimioterápicos que se asocian con más frecuencia son la doxorrubicina, 5-fluorouracilo, capecitabina, citarabina y docetaxel. Es más frecuente y severo en mujeres, pacientes de edad avanzada o con compromiso vascular periférico. Se presentan dos pacientes de sexo femenino. La primera con cáncer de ovario en tratamiento con doxorrubicina liposomal que presentó eritrodisestesia luego del quinto ciclo de quimioterapia. La segunda paciente con diagnóstico de cáncer de mama que recibió tratamiento con capecitabina presentando síntomas luego del segundo ciclo de quimioterapia. El interés de la presentación es la consulta a dermatología por un síndrome que constituye un efecto adverso que potencialmente limita el uso de determinados antineoplásicos. Sin embargo, educando al paciente, con intervenciones farmacológicas y ajuste de dosis, es posible aliviar los síntomas continuando una terapéutica efectiva (AU)

Erythrodysesthesia, or hand foot syndrome, is a side effect related to some chemotherapeutic agents. It is characterized by a prodrome of palmoplantar dysesthesia followed by burning pain with edema and erythema on well-defined and symmetrical plaques, 2-4 days later. Doxorubicin, 5-fluorouracil, capecitabine, cytarabine and docetaxel are the most frequently associated chemotherapy drugs. Women, elderly or peripheral vascular compromise patients are more frequent and severe affected. Two female patients are reported. The first patient with ovarian cancer in treatement with liposomal doxorrubicin developed erythrodysesthesia after the fifth cycle of chemotherapy. Meanwhile the second patient diagnosed with breast cancer in treatment with capecitabine developed it after the second cycle of chemotherapy. The interest of this report is the dermatological consultation about a side effect syndrome which potentially limits the prescription of certain antineoplastic drugs. However, patients can continue specific treatment by indicating dose adjustment and prescribing medicine to relieve the symptoms (AU)

Scrotal Erythema Associated with Sorafenib Therapy in a Patient with Hepatocellular Carcinoma / 대한피부과학회지

Sorafenib is an oral, multi-targeted tyrosine kinase inhibitor with anti-angiogenic and anti-proliferative activity. It is approved for the treatment of unresectable hepatocellular and advanced renal carcinomas. Cutaneous toxicity is relatively common in patients receiving sorafenib. The most frequent cutaneous side effect is the hand-foot syndrome. Other adverse skin reactions include facial erythema, acral erythema, erythema multiforme, subungual splinter hemorrhage, stomatitis, and alopecia. In Korea, two cases of scrotal and perianal dermatitis after sorafenib therapy were reported. We report a 54-year-old male patient with a 2-week history of scrotal eczema who had been treated for chronic hepatitis type B, liver cirrhosis, and hepatocellular carcinoma. After 2 weeks of oral sorafenib (800 mg/day) administration, thick, scaly patches appeared on his scrotum. A skin biopsy specimen from these lesions revealed superficial dermal perivascular lymphocytic and neutrophilic infiltration, and dilatation of the lymphatics in the superficial dermis. The lesions improved after treatment with a topical and systemic steroid for 2 weeks. Herein, we report a rare case of scrotal erythema associated with sorafenib.

Development and Validation of the Korean Version of Hand-Foot Skin Reaction and Quality of Life Questionnaire (HF-QoL-K)

Given the growing number of cancer patients and the resulting increase in the administration of chemotherapeutic agents, convenient and effective methods for measuring the symptoms and quality of life associated with the hand-foot syndrome (HFS) are needed. Therefore, the aim of this study was to develop and validate the Korean version of the hand-foot skin reaction and quality of life questionnaire (HF-QoL-K), comprising a 20-item symptom domain and an 18-item daily activity domain. After we developed the HF-QoL-K, 209 Korean patients with gynecologic cancer who were undergoing chemotherapeutic agents relating the HFS were asked to fill in the questionnaire. The content validity, internal consistency reliability, and test-retest reliability were evaluated. The internal validity index, Cronbach’s alpha coefficient, and intra-class correlation coefficient of the HF-QoL-K were 0.90, 0.958, and 0.825 (95% confidence interval [CI], 0.774–0.865), respectively. The scatter plot (Pearson correlation coefficient, 0.826) and the Bland-Altman plot for test-retest reliability were also acceptable. The HF-QoL-K instrument is a valid and reliable questionnaire for the measurement of the symptoms and quality of life in Korean cancer patients suffering HFS.

Serious stomatitis and esophagitis: a peculiar mucous reaction induced by pegylated liposomal doxorubicin

Pegylated liposomal doxorubicin is an important antineoplastic agent with activity in a variety of solid tumors. It has a totally different profile of pharmacokinetics and toxicity compared with doxorubicin. It rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in many kinds of mucocutaneous reactions, including palmar-plantar erythrodysesthesia, diffuse follicular rash, intertrigo-like eruption, new formation of melanotic macules, stomatitis and radiation recall dermatitis. We present a rare case of multiple myeloma who immediately developed serious stomatitis and esophatitis associated with minor palmar-plantar erythrodysesthesia after a single course of pegylated liposomal doxorubicin.