19 de novembro de 2020


 O livro Guia para Protocolos de Oncologia na Prática Clínica Volume 1 disponível no https://lnkd.in/djwkMqG apresenta uma descrição detalhada para 112 protocolos de oncologia com as seguintes informações: Indicações. Exames. Exames antes de cada ciclo. Regime terapêutico do protocolo detalhado [Dias, Medicamentos. Dose. Diluente. Diluição. Infusão. Ciclo. Tratamento anterior. Tratamento subsequente. Risco emético. Pré-QT. Ordem de infusão. Risco extravasamento. Medidas de suporte. Medicação pós-QT em casa. Pontos de atenção] Informações clínicas. Dose máxima tolerada (DMT). Ajuste de dose nas toxicidades hematológicas. Reações adversas do protocolo. Ajuste de dose nas toxicidades não-hematológicas. Interações medicamentosas. Riscos ocupacionais. Detalhes da administração. Tratamento do extravasamento. ANEXOS Ajuste de dose na disfunção renal e hepática Diretrizes em antieméticos MASCC/ESMO Cuidados gerais na administração dos medicamentos Incompatibilidade de via na infusão dos medicamentos Protocolos de dessensibilização Referências bibliográficas #oncologia #farmaciahospitalar #anticorpomonoclonal #nivolumabe

Colutório de DEXAmetasona no tratamento da mucosite oral no protocolo Everolimo + Exemestano (E-poster SEFH 2018)


 

14 de agosto de 2020

O PAPEL DO BCG NO CONTROLE DA EXPRESSAO DOS GENES PD1 E PDL1 EM ESTUDO IN VITRO DE CARCINOMA UROTELIAL DE BEXIGA

Denis Reis Morais, Vanessa Guimarães , Nayara Viana, Sabrina Thalita Reis , Iran Amourin Silva, Ruan Pimenta, Gabriel A G D dos Santos , Cristina Massoco, Katia Ramos Moreira Leite

Universidade Anhembi Morumbi – Faculdade de medicina - Sao Paulo - Brasil, Faculdade de Medicina da Universidade de São Paulo - Sao Paulo - Brasil

Introdução e objetivo:

A imunoterapia com o uso do Bacilo de Calmet Guerin (BCG) é o tratamento mais eficaz para o carcinoma urotelial (CUB) superficial de bexiga, diminuindo principalmente o número de recidivas, característica da neoplasia. Novas drogas foram desenvolvidas recentemente com alta atividade na estimulação do sistema imunológico, bloqueando os mecanismos de escape adquiridos pelas neoplasias que são a expressão de PD1 e PDL1. O mecanismo de ação do BCG ainda não foi totalmente elucidado e nossa hipótese é que possa atuar no controle de expressão dessas proteínas. Assim, nosso objetivo á a avaliação da expressão de PD1 e PDL1 em estudo in vitro do carcinoma urotelial de bexiga tratado com BCG.


Método:
Cultura de células de carcinoma urotelial de bexiga de baixo grau, recidivante, RT4 foi tratada com 3 concentrações de BCG, 5, 10 e 20 bacilos/célula tumoral. Após 4 e 24 horas, o RNA foi extraído e os níveis de expressão de PD1 e PDL1 foram avaliados pela reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR).


Resultados:
Após 4 horas de exposição ao BCG observamos um aumento da expressão dos genes PD1 e PDL-1 proporcional ao número de bacilos/célula tumoral quando comparado ao grupo controle. O aumento da expressão de PD1 nas células tratadas na concentração de 20:1 foi significativamente maior comparado ao grupo tratado com 5:1 (p= 0,0203).
No experimento de 24 horas de tratamento houve uma pequena redução na expressão de PD1 e PDL1 em relação ao controle, sendo ainda observado uma redução significativa entre o grupo de células tratada com 5:1 e o grupo 20:1 (p= 0,0232).


Conclusão:
Nossos resultados apontam um papel do BCG na regulação da expressão dos genes PD1 e PDL1 na qual a concentração de bacilos e o tempo de exposição parecem influenciar nesse mecanismo. Esses dados são inéditos e nos proporcionam uma melhor compreensão sobre o mecanismo de ação do BCG no tratamento do CUB.

Palavras Chave

PD1, PDL1, câncer de bexiga


Disponível em: www.congressourooncologia.com.br



5 de agosto de 2020

THALIDOMIDE ADMINISTRATION THROUGH A NASOGASTRIC TUBE

Asif Yusuf*, Aujla Harjinder, Correa West Joanna. Birmingham Children’s Hospital

Introduction LA, 15 year old female diagnosed with tuberculosis meningitis (TBM). General paediatric team recommended, in combination with existing adjunctive therapy, initiation of Thalidomide, a non-formulary drug.Challenge Administration of medication, for LA, was via a nasogastric tube. The cytotoxic nature of Thalidomide compounded with the lack of information from Celgene, the manufacturer of the only licensed Thalidomide in the United Kingdom (UK) that supplied oral capsules, provided numerous issues for administration. In addition, TBM was an unlicensed indication for Thalidomide. 

Outcome Approval through the Drug and Therapeutics Committee (DTC) was gained. Upon investigating into previous use at the trust, another patient had received Thalidomide for TBM in 2014, this was requested from the same consultant, however on that occurrence there was ease of administration through the oral route so the licensed oral capsules were used. Combined with this previous case and a thorough literature search, a dose was calculated of 200 mg (3 mg/kg once a day), which was agreed by the general paediatrics team. 

An unlicensed oral tablet formulation was sourced from another manufacturer in the UK. Crushing syringes were sourced to ensure the ‘crushing and dispersing process’ would occur in a closed system. The relevant forms for Thalidomide initiation were completed by the requesting consultant, with the patient and family advised on the appropriate pregnancy prevention measures. An administration guide via feeding tubes was developed for the nursing team. 

Steps included: wearing gloves and apron, using a crushing syringe to crush the Thalidomide tablet in a closed system, drawing 20 ml of water from a medicine pot into the crushing syringe, agitating the syringe to disperse the tablet, using the appropriate ENFIT adaptor to administer the dispersed medication into the feeding tube and disposing of appropriate waste into cytotoxic and clinical waste. 

Incorporated into this, a safety information leaflet for staff was developed, also for the nursing team, detailing the appropriate ward storage (controlled drugs cupboard) and handling measures, stressing the importance of the teratogenic nature of Thalidomide. The nursing team on the relevant ward, caring for LA, were counselled on and supplied with the guidance that was produced for them. A brief pharmacy guide was developed, detailing to the pharmacy team, the teratogenic nature of Thalidomide along with the special storage conditions (controlled drugs cupboard) and handling measures. 

The pharmacy team were informed of the case and guidance was sent out, to ensure that the correct safety measures were in place. Prior to dispensing, dispensing staff and screening pharmacists were asked to complete a consent form, in order to dispense/screen prescriptions for Thalidomide. Dispensing took place as per cytotoxic medications, with Thalidomide delivered in the relevant yellow sealed bags. Moving on A Thalidomide policy was drafted and will be submitted to the DTC for approval. Once approved, this will be available for the medical, nursing and pharmacy team, in the future. A pharmacy Thalidomide folder was created, that would house the policy and all the relevant forms required for audit.

Archives of Disease in Childhood 2018:103(2).

19 de julho de 2020

Topical aloe vera for the treatment of cetuximab-related acneiform rash in colorectal cancer: A case report

Mustafa Gu¨rbu¨z, Faculty of Medicine, Department of Medical Oncology, Ankara University, Ankara TR06100, Turkey. 

Email: drgurbuz123@gmail.com

Abstract
 
Introduction: Colorectal cancer is one of the most common cancers in the world. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor which provides survival benefit when combined with chemotherapy in RAS wild type metastatic colorectal cancer. Cutaneous toxicities associated with cetuximab have a significant impact on patient quality of life, treatment continuation and healthcare resource utilization. 

Case report: A 60-year-old male patient presented with fatigue, weight loss and abdominal pain. Two closely located malignant polypoid lesions were detected in the sigmoid colon, and pathological examination revealed colonic adenocarcinoma.

Management and outcome: Thorax, abdominal and pelvic computed tomography showed metastases. FOLFOX chemotherapy and cetuximab were started. The patient developed acneiform rash firstly in his face, although prophylactic vitamin K1 0.1% containing cream was given. He was given mild potency topical corticosteroid and doxycycline. The lesions progressed to his front and back body. He did not want to use topical vitamin K1 cream, topical steroid and doxycycline tablets. Instead, he wanted to use aloe vera extract which he produced from the leaves of the plant. Patient’s lesions were regressed significantly.

Discussion: The most common and earliest skin toxicity is acneiform rash which affects 60 to 80% of the patients. In this case, cetuximab-related severe acneiform rash was effectively treated by topical aloe vera. Topical aloe vera may be used in the management of cetuximab-related cutaneous toxicities without any side effect. Here, we have presented a case of cetuximab-related acneiform rash which regressed by topical aloe vera. Skin lesions on the body, face and neck are common side effects of cetuximab. These side effects generally occur in the second week of the treatment and regress when the treatment is discontinued.11 The common cutaneous toxicities include xerosis (dry skin), fissures, pruritus, eczema, skin infections and urticaria; nail conditions such as paronychia (suppurative inflammation around the nails) and hair-growth abnormalities, including trichomegaly. The most common and earliest skin toxicity is acneiform rash which affects 60 to 80% of the patients.8 Our patient developed acneiform rash at first week and progressed to maximum level at second week (Naranjo score: 7).

Conclusion In this case, cetuximab-related severe acneiform rash was effectively treated by topical aloe vera. Because it is crucial to give cetuximab without any dose modification and treatment delay, topical aloe vera may be used in the management of cetuximab-related cutaneous toxicities without any side effect. Prospective controlled studies may be designed to test this beneficial effect.

Keywords Colorectal cancer, cetuximab, aloe vera

J Oncol Pharm Practice

16 de julho de 2020

Tabela informativa da administração de medicamentos pela via subcutânea direta ou contínua


Serviço de Farmácia. Hospital Universitário Antonio Pedro - Niterói (RJ), Brasil 

Objetivo: Elaborar uma tabela de medicamentos que podem ser utilizados via SC. A ANVISA não definiu estas informações nas bulas dos medicamentos. Existem diversos medicamentos que podem ser administrados pela via subcutânea, mas ainda é necessária a realização de novos estudos para avaliar a segurança e a efetividade de outros grupos farmacológicos e assegurar uma prática baseada em evidência. A administração de medicações via SC tem duas denominações: administração intermitente (intermittent SC injection-ISCI) e contínua (continuous SC injectionCSCI). A administração de grande volume de fluidos é denominada hipodermóclise (HDC). 

Métodos: Realizou-se em maio de 2018, busca em sites especializados de hospitais universitários e para os seguintes descritores: hipodermóclise, médicaments administrés régulièrement par voie sous-cutanée, subcutânea, soins palliatifs par voie sous-cutanée. 

Resultados: Registrados na Suiça, Inglaterra, França, Alemanha uso via subcutânea: Alfentanila, Amicacina, Atropina, Buprenorfina, Ceftriaxona, Clonazepam, Dexametasona, Fenobarbital, Fentanila, Haloperidol, Hidromorfona, Hioscina, Ketamina, Ketorolaco, Levomepromazina, Meperidina, Metadona, Metoclopramida, Midazolam, Morfina, Octreotida, Ondansetrona, Oxicodona, Papaverina, Petidina, Prometazina, Ranitidina, Tramadol. Registrados na Suiça para uso via subcutânea: Alfainterferona, Atropina, Butilescopolamina, Clonidina, Citarabina, Dexferroxamina, Dexametasona, Efedrina, Epinefrina, Filgrastim, Glucagon, Imunoglobulina, Lenograstim, Metadona, Metilergometrina, Morfina, Nalbufina, Naloxona, Neostigmina, Octreotida, Petidina, Salbutamol, Tramadol, Vitamina B6, Vitamina B12. Relatos na literatura uso SC: Alentuzumabe, Alfentanila, Amicacina, Buprenorfina, Cefepima, Ceftriaxona, Clodronato, Clonazepam, Clorazepato, Desmopressina, Diclofenaco, Ertapenem, Esomeprazol, Fenobarbital, Fitomenadiona, Fentanila, Fludarabina, Furosemida, Granisetrona, Haloperidol, Hidromorfona, Ketamina, Ketorolaco, Levomepromazina, Mesna, Metotrexato, Metilprednisolona, Metoclopramida, Omeprazol, Ondansetrona, Ranitidina, Sufentanila, Teicoplanina, Tobramicina. 

Conclusão: A administração de medicamentos e soluções pela via subcutânea é uma alternativa segura e eficaz.

Revista Brasileira de Terapia Intensiva. Suplemento I. 2018. Resumos dos trabalhos científicos apresentados no XXIII CONGRESSO BRASILEIRO DE MEDICINA INTENSIVA. São Paulo. 2018.



15 de julho de 2020

Experiencia de uso de brentuximab vedotina en monoterapia o en combinación con bendamustina en linfoma de Hodgkin y linfoma anaplásico de células grandes


Conesa Nicolás E, Martínez Penella M, Gutiérrez-Meca Maestre MD, Mira Sirvent MC


Servicio de Farmacia. Hospital General Universitario Santa Lucía. Cartagena. Murcia (España) Elena Conesa Nicolás – Hospital General Universitario Santa Lucía (Servicio de Farmacia) – C/Mezquita, s/n – 30202 Cartagena. Murcia (España) elenalbs@hotmail.com

RESUMEN

Objetivo: Analizar el uso de brentuximab vedotina (BV) en monoterapia o en combinación con bendamustina en el tratamiento de linfoma Hodgkin (LH) y linfoma anaplásico de células grandes (LACG) en recaída o refractario. Métodos: Estudio retrospectivo y multicéntrico de los pacientes con LH o LACG en recaída o refractarios tratados con BV hasta febrero de 2019. Se analizaron variables demográficas, de la patología (clínicas y analíticas), respuesta y efectos adversos (EA). Resultados: Se incluyeron 16 pacientes en dos grupos. Grupo 1 (BV en monoterapia, 10 pacientes): 6 hombres, 57,5 años (rango: 44-72). 7 pacientes presentaban LH y 3 LACG. Tras 4 ciclos, se obtuvieron 6 respuestas parciales (RP), 3 respuestas completas (RC) y un paciente refractario. Tasa respuesta objetiva (TRO) 90%. 5 pacientes en RP progresaron siendo la supervivencia libre de progresión (SLP) 4 meses (IC 95% 2,55-4,27). Un paciente en RC fue sometido a trasplante autólogo de progenitores hematopoyéticos (TAPH) y recibió BV en mantenimiento. Grupo 2 (en combinación con bendamustina, 6 pacientes): 4 hombres, 42 años (rango: 18-74). Tras 4 ciclos se obtuvieron 2 RP, 3 RC y 1 paciente refractario. TRO 83,33%. 1 paciente en RP progresó (SLP 3 meses). Los pacientes en RC pudieron beneficiarse de TAPH y mantenimiento con BV. En ambos grupos los EA principales fueron neuropatía (grado 3 en 2 pacientes) y alteraciones digestivas. Conclusiones: BV presenta buena actividad en monoterapia, logrando TRO elevadas. La combinación con bendamustina ha permitido aumentar la eficacia logrando respuestas más duraderas y nos ha permitido ofertar TAPH a pacientes no candidatos previamente. Se han reportado EA manejándose adecuadamente. Son necesarios más estudios para posicionar BV en la práctica clínica habitual.
Palabras clave: Brentuximab vedotina, bendamustina, linfoma de Hodgkin, linfoma anaplásico de células grandes, efectividad, seguridad.

Experience of use of brentuximab vedotin in monotherapy or combination with bendamustin in Hodgkin lymphoma and anaplastic large cell lymphoma

SUMMARY

Objective: To analyze the use of brentuximab vedotin (BV) in monotherapy or in combination with bendamustine in the treatment of relapsed or refractory Hodgkin’s lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Methods: Retrospective and multicenter study of patients with relapsed or refractory HL or ALCL treated with BV until February 2019. Demographic, pathological (clinical and analytical), response and toxicity variables were analyzed. Results: Sixteen patients were included in two groups. Group 1 (BV in monotherapy, 10 patients): 6 men, 57.5 years (range: 44-72). 7 patients presented HL and 3 ALCL. After 4 cycles, 6 partial responses (PR), 3 complete responses (CR) and one refractory patient were obtained. Objective response rate (ORR) 90%. 5 patients in PR progressed being progression-free survival (PFS) 4 months (95% CI 2.55-4.27). A patient in CR was submitted to autologous stem cell transplantation (ASCT) and received BV in maintenance. Group 2 (in combination with bendamustine, 6 patients): 4 men, 42 years (range: 18-74). After 4 cycles, 2 PR, 3 CR and 1 refractory patient were obtained. ORR 83.33%. 1 patient in PR progressed (PFS 3 months). The patients in CR could benefit from ASCT and maintenance with BV. In both groups, the main adverse effects (AE) were neuropathy (grade 3 in 2 patients) and digestive alterations. Conclusions: BV presents good activity in monotherapy, achieving high ORR. The combination with bendamustine has made it possible to increase efficiency by achieving more lasting responses and it has allowed us to offer ASCT to previously non-candidates. AE have been reported but they have been handled properly. Further studies are necessary to position BV in routine clinical practice.
Brentuximab vedotin, bendamustine, Hodgkin lymphoma, anaplastic large cell lymphoma, effectiveness, safety.
Rev. OFIL·ILAPHAR 2020 [first on line] / ORIGINAL / 1

18 de junho de 2020

Oral anticancer drugs: To crush or not to crush

Tine Van Nieuwenhuyse, Birgit Tans, David Devolder, Isabel Spriet.

Hospital Pharmacy Department, UZ Leuven, Leuven, Belgium. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium 

Objective/purpose: Healthcare professionals, involved in the daily care of cancer patients, are faced with the growing issue using oral anticancer drugs in patients experiencing swallowing difficulties. The lack of commercially available oral liquid dosing forms might compromise initiating or prolonging necessary therapies in this patient population. Pharmacists are often challenged to provide liquid alternatives for oral drugs that have solely been made commercially as a solid formulation; therefore, it is common practice to crush tablets or to prepare oral liquids from solid forms. When preparing liquids ex tempore, a number of requirements need to be fulfilled. In addition to chemical, physical and microbiological stability of the active ingredients, therapeutic and toxicological aspects should be the subject of review. The goal was to develop a guide for healthcare providers in order to assist them in providing scientific and up-to-date information for patients who are in need of special dosing forms.

Study design/methods: A literature search in PubMed/Medline was conducted. Also, the registration documents and relevant phase I and II data from the pharmaceutical industry, U.S. Food and Drug Administration and European Medicines Agency were used as a source of information. 

Results/key findings: An overview for healthcare providers was drafted. Sixty-two oral anticancer drugs that were available on the Belgian market at the moment of the development were included. 

Conclusion/recommendations: The development of a pocket guideline has increased the awareness and will be added to the standard of care as to improve safe medication use in patients with swallowing difficulties.

Selected abstracts presented at the XVI Symposium of the International Society of Oncology Pharmacy Practitioners April 26-29, 2017, Budapest, Hungary

J Oncol Pharm Practice 2017, Vol. 23 4(Supplement) 1–21.

4 de maio de 2020

Pseudocelulitis recurrente inducida por gemcitabina: descripción de un caso.

CALPE ARMERO P1, ESQUERDO GALIANA G1, PEIRÓ SOLERA R1, MARTÍNEZ TÉBAR MJ2

1 Hospital Clínica Benidorm. Alicante (España) 2 Hospital General de Elche. Alicante (España)

RESUMEN Introducción: Gemcitabina es un agente antineoplásico usado en el tratamiento de un gran número de neoplasias malignas. Está asociado frecuentemente a reacciones adversas cutáneas como prurito, rush o alopecia. Menos frecuentemente, se ha visto asociado a un cuadro llamado “pseudocelulitis”. En este estudio presentamos un caso de un paciente con pseudocelulitis recurrente tras tratamiento con gemcitabina. Descripción del caso: Paciente oncológico, con historia pasada de linfedema en miembros inferiores acude a consulta por cuadros recurrentes de celulitis en miembro inferior homolateral al brazo de infusión del fármaco gemcitabina. El paciente no presenta fiebre. Presenta eritema bien delimitado, edema con fóvea, caliente y con dolor a la palpación. En la analítica se obtienen valores normales, y no se observa evidencia de trombosis venosa profunda. Basado en los hallazgos clínicos, naturaleza aguda y recurrente de la patología, se llegó, por descarte, a un diagnóstico de pseudocelulitis inducida por gemcitabina. El cuadro fue tratado con antihistamínicos y antiinflamatorios no esteroideos. Al final del seguimiento, el paciente presentaba una notoria mejoría de los síntomas. Conclusión: En pacientes tratados con gemcitabina, que presenten episodios de celulitis, es importante establecer clínica y analíticamente, si se trata o no de una celulitis infecciosa. Ya que, de tratarse de un cuadro de pseudocelulitis, el tratamiento no se compone de antibióticos y el periodo de hospitalización será menor. 

Palabras clave: Pseudocelulitis, gemcitabina, adenocarcinoma de páncreas, celulitis, reacción adversa. 

SUMMARY Introduction: Gemcitabine is an antineoplastic agent used in the treatment of a large number of malignant neoplasms. It is frequently associated with adverse skin reactions such as pruritus, rush or alopecia. Less frequently, it has been associated with a condition called "pseudocellulitis". In this study, we present a case of a patient with recurrent pseudocellulitis after treatment with gemcitabine. Case description: Oncological patient, he had history of lymphedema in the lower extremity, is referred to consultation with complaint of recurrent cellulitis in the homolateral lower extremity from the infusion arm of gemcitabine. The patient does not have fever. It presents well-defined erythema, pitting edema, warmth and tenderness to palpation. Analytical values were normal, and evidence of deep vein thrombosis is not observed. Based on the clinical findings, acute and recurrent nature of the pathology, a diagnosis of pseudocellulitis induced by gemcitabine was reached. The patient was treated with antihistamines and nonesteroideal anti-inflammatory. At the end of the follow-up, the patient showed a marked improvement in symptoms. Conclusion: In patients treated with gemcitabine, who present episodes of cellulitis, it is important to establish clinically and analytically, whether or not it is an infectious cellulitis. Since it is a case of pseudocellulitis, the treatment is not composed of antibiotics and the period of hospitalization will be shorter. Recurrent gemcitabine-induced pseudocellulitis: a case report 

Key Words: Pseudocellulitis, gemcitabine, pancreas adenocarcinoma, cellulitis, adverse event.

Referência: Rev. OFIL·ILAPHAR 2020, 30;2:150-151

Miastenia gravis secundaria a pembrolizumab

MINARDI EP

Servicio de Farmacia Ambulatoria. Hospital Italiano de Buenos Aires y Depto. Farmacología y Toxicología. Instituto Universitario del Hospital Italiano. Buenos Aires (Argentina).

RESUMEN En los últimos años el avance de terapias dirigidas para tratamiento de enfermedades oncológicas ha ido en aumento exponencial. En este contexto, un nuevo grupo de anticuerpos monoclonales, que inhiben el receptor de muerte celular programada 1 han surgido como una efectiva primera línea de tratamiento para determinadas neoplasias. Pembrolizumab, un anticuerpo monoclonal humanizado, es una opción estándar para el tratamiento de enfermedades malignas avanzadas o metastásicas tales como mieloma múltiple pero, en lo que a seguridad respecta, investigaciones clínicas han descubierto diversos, impredecibles y graves eventos adversos relacionados con el sistema inmunológico. Se describe caso de un paciente oncológico con sospecha de miastenia gravis luego de haber recibido pembrolizumab 200 mg cada 3 semanas. 

Palabras clave: Miastenia gravis, pembrolizumab, receptor de muerte celular programada 1.

SUMMARY In recent years the development of anti-cancer target drugs therapy has been increasing exponentially. In this context, a monoclonal antibody group’s which inhibits the programmed cell death 1 receptor, has emerged as an effective frontline of treatment of certain neoplasms. Pembrolizumab, a humanized monoclonal antibody, is a standard option for the treatment of advanced and metastatic malignancies like multiple myeloma. However, clinical research has uncovered diverse, unpredictable and serious immune related adverse events that raise concerns regarding it's safety. Here we describe the case of an oncology patient with a suspected myasthenia gravis after receiving pembrolizumab 200 mg every 3 weeks. Miastenia gravis secondary to pembrolizumab Key Words: Myasthenia gravis, pembrolizumab, programmed cell death 1 receptor.

Referência: Revista OFIL·ILAPHAR 2020, 30;2:145-146

5 de março de 2020

Cytarabine ears – A side effect of cytarabine therapy

Divya Doval , Sanjeev Kumar Sharma, Meet Kumar, Vipin Khandelwal and Dharma Choudhary

Divya Doval, Department of Hematooncology and BMT, BLK Superspeciality Hospital, New Delhi 110005, India.

Email: divyadoval@yahoo.co.uk

Abstract Cytarabine, a pyramidine analog, is used for treating various hematological malignancies such as acute leukemias and lymphomas. Side effects of cytarabine are dose dependent and include bone marrow suppression, fever, cerebellar toxicity, cardiomyopathy, hepato-renal insufficiency, necrotizing enterocolitis, pancreatitis, acute respiratory distress, corneal toxicity and dermatological side effects. The dermatological side effects can be immediate or due to delayed hypersensitivity reactions. They have been attributed largely to release of cytokines. We present three such cases of delayed hypersensitivity to cytarabine affecting the ears bilaterally.

Case report

Case 1 A 41-year-old female, a case of acute myeloid leukemia (intermediate risk), was treated with 7+ 3 induction chemotherapy (cytarabine 100 mg/m2 for seven days by continuous infusion along with daunorubicin 60 mg/m2 for three days). On day 6 of chemotherapy, she developed erythema over one ear not associated with pain or itching (Figure 1), which subsequently spread to both ears, sparing of all other areas of face and body. She did not have any associated fever. 

Case 2 A 60-year-old lady was diagnosed to have acute myeloid leukemia (low risk). She was treated with 7+ 3 induction chemotherapy (cytarabine 100 mg/m2 for seven days twice daily along with daunorubicin 60 mg/m2 for three days). On day 8 of chemotherapy (few hours after the last dose), she developed erythema over both ears with associated itching and mild burning pain (Figure 2). There was no associated fever.

Case 3 A 42-year-old lady with acute myeloid leukemia received 7+3 induction (cytarabine 100 mg/m2 for seven days by continuous infusion along with daunorubicin 60 mg/m2 for three days). On day 7, she developed an erythematous rash on bilateral ear lobes associated with pain and itching.

Management and outcome 

Case 1 The patient subsequently developed neutropenic fever and was treated with broad spectrum antibiotics. Her repeat blood and urine cultures were sterile. The rash started reducing 48 h after cessation of chemotherapy and completely resolved within five days. 

Case 2 The rash and itching were treated with oral fexofenadine and resolved completely over next 72 h. This patient was re-challenged with high-dose cytarabine in the consolidation phase of her chemotherapy without recurrence of any dermatologic manifestations. 

Case 3 This patient was treated with topical hydrocortisone 1% ointment and oral analgesics. The rash turned to bluish purple by day 12 and then subsequently resolved by day 15. This study was approved by the hospital ethics committee and informed consent from patients was taken.

Discussion 

Cytarabine can cause various types of skin reactions. The typical cytarabine-induced skin rash develops 6– 12 h after the drug is started and resolves with cessation of therapy. Incidence of the cytarabine-induced systemic rash varies between 3 and 72% and is more commonly seen in patients receiving high doses of cytarabine.1 The generalized rash has also been reported with low doses and in both adults and children.1,2 It may manifest as maculopapular or morbilliform rash or as hand–foot syndrome, which presents as erythema of palms and soles, associated with pain, tingling and paresthesia, or it may involve trunk and extremities. Isolated involvement of ears has rarely been reported, with only nine cases reported.


J Oncol Pharm Practice 2020, Vol. 26(2) 471–473


13 de fevereiro de 2020

Comparación de las guías NCCN, ESMO y SEOM de 2016 para la prevención de las náuseas y vómitos por quimioterapia


Gutiérrez Lorenzo M., Mora Rodríguez B., Henares López A., Muñoz Castillo I.
Hospital Regional de Málaga

Objetivo: El propósito de este estudio es determinar si las guías más usadas en España difieren en sus recomendaciones con el fin de optimizar la profilaxis de uno de los efectos adversos más preocupantes de la quimioterapia en nuestro sistema de salud: las náuseas y vómitos inducidos por los antineoplásicos.

Material y métodos: Se analizaron las recomendaciones de las guías: Nacional Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) y Sociedad Española de Oncología Médica (SEOM) publicadas en el año 2016 para la prevención de la emesis por quimioterapia. Se elabora una base de datos tanto de los antineoplásicos parenterales como de los orales para identificar las diferencias en los siguientes puntos: número de niveles de riesgo emetógeno, número total de agentes antineoplásicos incluidos, número de agentes antineoplásicos que aparecen sólo en una de las guías, número de antineoplásicos que se clasifican en niveles de riesgo emetógeno distintos, número de agentes que se clasifican diferente dependiendo de la dosis que se prescriba, recomendaciones de la profilaxis a usar según los niveles de riesgo.

Resultados: Los principales puntos de discrepancia entre las clasificaciones de las guías ESMO y SEOM con respecto a la guía NCCN son los siguientes: En cuanto a los agentes antineoplásicos orales, la NCCN divide en 2 los niveles de riesgo de producir naúseas y vómitos: riesgo de moderado a alto y de mínimo a bajo; la ESMO y la SEOM hacen más distinción, dividen en 4 niveles (alto, moderado, bajo y mínimo). Sin embargo, las tres guías dividen en los mismos 4 niveles el riesgo emetógeno de los agentes antineoplásicos parenterales. En total, en la NCCN se observan 97 agentes antineoplásicos parenterales, de los cuales 53 (54.6%) y 27 (27,8%) no aparecen en la guía SEOM y ESMO respectivamente. También se compararon un total de 62 agentes antineoplásicos orales, de los que 48 (77.4%) y 22 (35.5%) no aparecen en la guía SEOM y ESMO respectivamente. Observamos también que del total de agentes parenterales 11 (11.3%) y 4 (4.1%) estaban clasificados en distintos niveles de riesgo emetógeno en la NCCN frente a la ESMO y a la SEOM, respectivamente.  Además, en la NCCN hay distinción en el riesgo de emesis dependiendo del rango de dosis en 8 antineoplásicos, mientras que en la SEOM Y ESMO sólo en 2 agentes. Por otra parte, en cuanto a los agentes profilácticos recomendados según los niveles de riesgo no hay discordancias significativas. 

Conclusiones: Aunque existen varios puntos de discrepancia entre las directrices de la ESMO, la SEOM y la NCCN, sobre todo en la clasificación, podemos concluir que hay una concordancia sustancial. La aplicación de estas recomendaciones a la práctica diaria nos permite periódicamente actualizar actualizar nuestro protocolo para minimizar la toxicidad emetógena de los tratamientos antineoplásicos.  Como tal, las guías están destinadas a ser novedosas, herramientas de alta calidad, lógicas, prácticas y útiles para el clínico. La meta es la optimización de la calidad de vida del paciente con el uso racional de los medios.

Referências: Anais do 14º CONGRESO SAFH SEVILLA 2017 - Sociedad Andaluza de Farmaceúticos de Hospitales y Centros Sociosanitarios.

4 de fevereiro de 2020

Oseltamivir combined with HIV drugs lopinavir and ritonavir the medications improved conditions in patients with severe 2019-nCoV infections

combination of flu and HIV medications may be able to treat severe cases of 2019-nCoV, the new coronavirus that has emerged in China, according to doctors in Thailand who have been caring for infected patients. The team’s approach, which used large doses of the flu drug Oseltamivir combined with HIV drugs lopinavir and ritonavir, improved the conditions of several patients at the Rajavithi Hospital in Bangkok.

“This is not the cure, but the patient’s condition has vastly improved,” Rajavithi Hospital’s Kriangsak Atipornwanich says of one 70-year-old Chinese woman from Wuhan, according to Reuters. “From testing positive for 10 days under our care, after applying this combination of medicine the test result became negative within 48 hours.”

Thailand has so far recorded 19 cases of coronavirus, Reuters reports, making it the country with the greatest number of infections in Southeast Asia. Eight patients have recovered, while the rest are still undergoing treatment. Officials say that the country’s health ministry would meet today (February 3) to discuss the new treatment for severe cases. “We still have to do more study to determine that this can be a standard treatment,” Atipornwanich tells reporters.

Other countries have also showed interest in using HIV drugs against the new coronavirus. China’s National Health Commission recently began recommending lopinavir and ritonavir (sold together by Illinois-based pharma AbbVie as Kaletra), according to Fierce Pharma. AbbVie has pledged to donate about $1.5 million worth of Kaletra for the effort.

A randomized controlled clinical trial is now underway in China to test the anti-HIV drugs’ efficacy, according to a study published last week (January 24) in The Lancet. Scientists in Hong Kong will also likely test these drugs in patients alongside immune system–boosting medications, Hong Kong University microbiologist Yuen Kwok-Yung tells Science.

Other treatments being considered by national governments and pharma companies include Gilead Sciences’s remdesivir, a drug that was designed to treat Ebola but failed efficacy tests. “Gilead is working closely with global health authorities to respond to the novel coronavirus (2019-nCoV) outbreak through the appropriate experimental use of our investigational compound remdesivir,” the company’s Chief Medical Officer Merdad Parsey says in a statement.

Massachusetts-based Moderna Therapeutics, meanwhile, is collaborating with the US National Institute of Allergy and Infectious Diseases to develop an mRNA vaccine, Fierce Pharma reports.
Catherine Offord is an associate editor at The Scientist. Email her at cofford@the-scientist.com.

27 de janeiro de 2020

Novo coronavírus (2019-nCoV)


Introdução

Diante da emergência por doença respiratória, causada por agente novo coronavírus (2019-nCoV), conforme casos detectados na cidade de Wuhan, na China e considerando-se as recomendações da Organização Mundial de Saúde (OMS), as equipes de vigilância dos estados e municípios, bem como quaisquer serviços de saúde, devem ficar alerta aos casos de pessoas com sintomatologia respiratória e que apresentam histórico de viagens para areas de transmissão local nos últimos 14 dias. Mais informações a respeito podem ser obtidas no link na Organização Mundial da Saúde (https://www.who.int/emergencies/diseases/novel-coronavirus-2019).

Sinais e sintomas

Os sinais e sintomas clínicos referidos são principalmente respiratórios. Por exemplo: febre, tosse e dificuldade para respirar.

Definição de transmissão local

Definimos com transmissão local, a confirmação laboratorial de transmissão do 2019-nCoV entre pessoas com vínculo epidemiológico comprovado. Geralmente para os coronavirus (SARS e MERS) essa transmissão ocorre entre os contatos próximos e profissionais de saúde.

Notificação

Os casos suspeitos, prováveis e confirmados devem ser notificados de forma imediata (até 24 horas) pelo profissional de saúde responsável pelo atendimento, ao Centro de Informações Estratégicas de Vigilância em Saúde Nacional (CIEVS) pelo telefone (0800 644 6645) ou e-mail (notifica@saude.gov. br). As informações devem ser inseridas na ficha de notificação (http://bit.ly/2019-ncov) e a CID10 que deverá ser utilizada é a: B34.2 – Infecção por coronavírus de localização não especificada.

Procedimentos para diagnóstico laboratorial

A. Coleta
Usar equipamento de proteção individual (EPI) adequado, que inclui luvas descartáveis, avental e proteção para os olhos ao manusear amostras potencialmente infecciosas bem como uso de máscara N95 durante procedimento de coleta de materiais respiratórios com potencial de aerossolização (aspiração de vias aéreas ou indução de escarro).

A realização de coleta de amostra, está indicada sempre que ocorrer a identificação de caso suspeito.
Orienta-se a coleta de aspirado de nasofaringe (ANF) ou swabs combinado (nasal/oral) ou também amostra de secreção respiratória inferior (escarro ou lavado traqueal ou lavado bronca alveolar).
 
É necessária a coleta de 2 amostras na suspeita de 2019-nCoV. As duas amostras serão encaminhadas com urgência para o LACEN. O LACEN deverá entrar em contato com a CGLAB para solicitação do transporte. Uma das amostras será enviada ao Centro Nacional de Influenza (NIC) e outra amostra será enviada para análise de metagenômica.

B. Transporte
O Ministério da Saúde - MS, disponibiliza o transporte das amostras via Voetur, que em casos de emergência trabalha em esquema de plantão, inclusive nos finais de semana. O Lacem deverá realizar a solicitação do transporte, mediante requerimento padrão, que deve ser enviado ao e-mail: transportes.cglab@saude.gov.br  e clinica.cglab@saude.gov.br.

As amostras devem ser mantidas refrigeradas (4-8°C) e devem ser processadas dentro de 24 a 72 horas da coleta. Na impossibilidade de envio dentro desse período, recomenda-se congelar as amostras a -70°C até o envio, assegurando que mantenham a temperatura.  A embalagem para o transporte de amostras de casos suspeitos com infecção por 2019-nCoV devem seguir os regulamentos de remessa para Substância Biológica UN 3373, Categoria B.

C. Priorização
Os testes para o 2019-nCoV devem ser considerados apenas para pacientes que atendam à definição de caso suspeito, uma vez descartada a infecção por Influenza.
Avaliação dos contactantes

Deverá ser realizada a busca ativa de contatos próximos (familiares, colegas de trabalho, entre outros, conforme investigação) devendo ser orientados, sob a possibilidade de manifestação de sintomas e da necessidade de permanecer em afastamento temporário em domicílio, mantendo distância dos demais familiares, além de evitar o compartilhamento de utensílios domésticos e pessoais, até que seja descartada a suspeita. Orientar que indivíduos próximos que manifestarem sintomas procurem imediatamente o serviço de saúde.


Atendimento do caso suspeito Para pessoas que preencham a definição de caso suspeito

ISOLAMENTO 
1. Paciente  deve utilizar mascára cirúrgica a partir do momento da suspeita e ser mantido preferencialmente em  quarto privativo. 
2. Profissionais devem utilizar medidas de precaução padrão, de contato e de gotículas (mascára cirúrgica, luvas, avental não estéril e óculos de proteção). Para a realização de procedimentos que gerem aerossolização de secreções respiratórias como intubação, aspiração de vias aéreas ou indução de escarro, deverá ser utilizado precaução por aerossóis, com uso de máscara N95.

AVALIAÇÃO
1. Reaizar coleta de amostras respiratórias. 
2. Prestar primeiros cuidados de assistência.

ENCAMINHAMENTO 
1. Os casos graves devem ser encaminhados a um  Hospital de Referência para Isolamento e tratamento. 
2. Os casos leves devem ser acompanhados pela Atenção Primária em Saúde (APS) e instituídas  medidas de precaução domiciliar.

No atendimento deve-se levar em consideração os demais diagnósticos diferenciais pertinentes e o adequado manejo clínico. 

Em caso de suspeita para Influenza não retardar o início do tratamento com Oseltamivir, conforme protocolo de tratamento de Influenza:

http://bvsms.saude.gov.br/bvs/publicacoes/protocolo_tratamento_influenza_2017.pdf.