Percepção dos profissionais de enfermagem sobre manejo de reação infusional a antineoplásicos: estudo qualitativo / Perception of nursing professionals on the management of infusion reactions to antineoplastics: qualitative study

Identificar a percepção dos profissionais de enfermagem sobre o manejo de reação infusional imediata a antineoplásicos. Método: Trata-se de um estudo descritivo de caráter exploratório com abordagem qualitativa realizado em um hospital no Rio Grande do Sul. Resultados: Todos os participantes afirmaram saber identificar uma reação infusional. Após a identificação da reação, nota-se que a maioria obedeceu a uma ordem de condutas a serem realizadas. Quanto aos cuidados para prevenção das reações infusionais, a maioria dos participantes mencionou a administração de medicamentos pré-quimioterápicos, como antialérgicos e antieméticos. Conclusão: Os achados demonstram que a maioria dos profissionais sabe reconhecer e manejar, porém há a necessidade de treinamentos e padronização das ações.(AU)

To identify the perception of nursing professionals about the management of immediate infusion reactions to antineoplastic drugs. Method: This is a descriptive, exploratory study with a qualitative approach carried out in a hospital in Rio Grande do Sul. Results: All the participants said they knew how to identify an infusion reaction. After identifying the reaction, it was noted that the majority followed an order of conduct to be carried out. As for precautions to prevent infusion reactions, most of the participants mentioned the administration of pre-chemotherapy drugs, such as anti-allergic and anti-emetic drugs. Conclusion: The findings show that most professionals know how to recognize and manage them, but there is a need for training and standardization of actions.(AU)

Identificar la percepción de los profesionales de enfermería sobre el manejo de las reacciones infusionales inmediatas a medicamentos antineoplásicos. Método: Se trata de un estudio descriptivo, exploratorio, con abordaje cualitativo, realizado en un hospital de Rio Grande do Sul. Resultados: Todos los participantes afirmaron saber identificar una reacción a la infusión. Después de identificar la reacción, la mayoría siguió un orden de conducta. En cuanto a las precauciones para prevenir las reacciones a la infusión, la mayoría de los participantes mencionó la administración de fármacos prequimioterápicos, como antialérgicos y antieméticos. Conclusión: Los hallazgos muestran que la mayoría de los profesionales saben reconocerlas y manejarlas, pero es necesaria la formación y la estandarización de actuaciones.(AU)

Uso da laserterapia de baixa intensidade na prevenção e tratamento da mucosite oral induzida por tratamentos antineoplásicos / Use of low-intensity lasertherapy in the prevention and treatment of oral mucositis induced by antineoplastic treatments

Sabe-se que para o combate de células cancerígenas, é imprescindível a submissão de pacientes oncológicos a tratamentos antineoplásicos, sessões de quimioterapia e radioterapia são as terapêuticas mais utilizadas em pacientes neoplásicos, sendo capazes de originar inúmeras reações adversas, como a mucosite oral, que é considerada um dos principais efeitos adversos do tratamento com quimioterapia e radioterapia. A laserterapia vem sendo considerada um grande aliado na prevenção e tratamento da mucosite, visto que de forma preventiva retarda o aparecimento desta condição, e de forma terapêutica proporciona alívio da dor, além de reduzir a gravidade da mucosite oral. Dessa forma, a presente revisão de literatura teve por objetivo denotar os benefícios da laserterapia de baixa intensidade na prevenção e tratamento da mucosite oral induzida por tratamentos antineoplásicos. Para a confecção deste trabalho, foram pesquisados artigos científicos publicados entre 2012 e 2022, nas bases de dados PubMed, Portal BVS, Scielo e google acadêmico, nos idiomas inglês e português. Como resultado foram encontrados 59 trabalhos, onde após leitura dos títulos e resumos, e do tipo de estudo, foram excluídos 32 artigos. Sendo 27 selecionados para leitura integral do texto, onde dentre eles somente 19 se encaixaram nos critérios de inclusão e foram utilizados neste trabalho. Portanto, conclui-se que a literatura mostra que embora haja bastante discussão, a maior parte dos estudos mostram evidências que a laserterapia de baixa intensidade possui muitos benefícios na prevenção e no tratamento da mucosite oral devido sua capacidade moduladora nos eventos metabólicos por meio de processos fotofísicos e bioquímicos(AU)

It is known that in order to fight cancer cells, it is essential to submit cancer patients to antineoplastic treatments, chemotherapy and radiotherapy sessions are the most used therapies in cancer patients, being capable of causing numerous adverse reactions, such as oral mucositis, which is considered one of the main adverse effects of chemotherapy and radiotherapy treatment. Laser therapy has been considered a great ally in the prevention and treatment of mucositis, since in a preventive way it delays the onset of this condition, and in a therapeutic way it provides pain relief, in addition to reducing the severity of oral mucositis. Thus, the present literature review aims to denote the benefits of low-level laser therapy in the prevention and treatment of oral mucositis induced by antineoplastic treatments. For the preparation of this work, scientific articles published between 2012 and 2022 were searched in PubMed, Portal BVS, Scielo and academic google databases, in English and Portuguese. As a result, 59 studies were found, where after reading the titles and abstracts, and the type of study, 32 articles were excluded. 27 were selected for full text reading, among which only 19 met the inclusion criteria and were used in this work. Therefore, it is concluded that the literature shows that, although there is a lot of discussion, most studies show evidence that low-level laser therapy has many benefits in the prevention and treatment of oral mucositis due to its modulating capacity in metabolic events through processes photophysical and biochemical(AU)

Alterações osteometabólicas em pacientes em tratamento antineoplásico: revisão de escopo / Osteometabolic changes in patients under antineoplastic treatment: scoping review

Objetivo: sintetizar as principais evidências acerca das alterações osteometabólicas presentes nos pacientes em tratamento antineoplásico. Métodos: trata-se de uma revisão de escopo, seguindo a metodologia do Instituto Joanna Briggs, nas bases de dados PubMed/MedLine, Cochrane Library, LILACS, The British Library e Google Scholar. A revisão está protocolada no Open Science Framework. Resultados: muitos antineoplásicos possuem efeito na arquitetura óssea, reduzindo sua densidade, tais como moduladores seletivos de receptores de estrogênio, inibidores da aromatase, terapia de privação androgênica, e glicocorticoides. Para evitar tais desfechos, o tratamento e prevenção podem ser realizados pela suplementação de cálcio e vitamina D, exercícios físicos, uso de bifosfonatos, denosumab, e moduladores seletivos do receptor de estrogênio. Conclusão: pessoas com maior risco de desenvolver câncer também possuem maior risco de osteopenia e osteoporose, quando processo já estabelecido e em tratamento antineoplásico, devido ao compartilhamento de fatores de risco. Torna-se evidente a necessidade da densitometria óssea nos pacientes em tratamento contra o câncer para de prevenção e promoção de saúde óssea nesses pacientes, além de mais pesquisas com alto nivel de evidência para subsidiar tal uso.

Objective: To summarize the main evidence regarding osteometabolic changes in patients undergoing antineoplastic treatment. Methods: This is a scoping review, following the methodology of the Joanna Briggs Institute, using PubMed/MedLine, Cochrane Library, LILACS, The British Library, and Google Scholar. This review is registered in the Open Science Framework. Results: Many antineoplastics affect bone architecture by reducing its density, such as selective estrogen receptor modulators, aromatase inhibitors, androgen deprivation therapy, and glucocorticoids. To avoid such outcomes, treatment and prevention can be achieved by calcium and vitamin D supplementation, physical exercise, use of bisphosphonates, denosumab, and selective estrogen receptor modulators. Conclusion: people at a higher risk of developing cancer also have a higher risk of osteopenia and osteoporosis when the process is already established and undergoing antineoplastic treatment because of the grouping of risk factors. The need for bone densitometry in patients undergoing cancer treatment to prevent and promote bone health in these patients is evident, in addition to more research with a high level of evidence to support such use.

Percepção do enfermeiro sobre os cuidados relacionados ao extravasamento de drogas antineoplásicas / Percepción de profesionales de enfermería sobre los cuidados relacionados con la extravasación de medicamentos antineoplásicos / Perception of the nursing professional about the care related to extravasation of antineoplastic drugs

Introdução: O uso de quimioterapias antineoplásicas atuando a nível celular com objetivo de tratar as neoplasias malignas, pode levar ao surgimento da toxicidade dermatológica, ocasionada pelo extravasamento, que consiste em um dano tecidual decorrente da infiltração, por via endovenosa, dos quimioterápicos aos tecidos circunvizinhos do local puncionado, necessitando de uma atuação profissional rápida e efetiva para evitar desfechos desfavoráveis para o paciente. Objetivo: Compreender a percepção do enfermeiro sobre os cuidados relacionados ao extravasamento de drogas antineoplásicas. Método: Trata-se de um estudo de campo, descritivo-exploratório com abordagem qualitativa, realizado com quinze enfermeiros que atuam no ambulatório e enfermarias da oncologia adulto de uma instituição hospitalar filantrópica localizada em Recife/Pernambuco, Brasil. Os dados foram coletados entre janeiro e dezembro de 2020 através de entrevista e passaram por análise de conteúdo temática-categorial. Resultados: Emergiram duas categorias. Cuidados preventivos: da identificação dos fatores de riscos à educação do paciente e equipe de saúde; Cuidados diretos: da identificação da ocorrência ao gerenciamento institucional do evento. Conclusão: Compreendeu-se que a percepção do enfermeiro destaca a importância do planejamento da assistência, incluindo a intervenção imediata, o registro do evento e o acompanhamento do paciente após o extravasamento, como forma de realizar um cuidado especializado e com maior segurança.

Introducción: El uso de quimioterapias antineoplásicas que actúan a nivel celular con el objetivo de tratar neoplasias malignas puede conducir a la aparición de toxicidad dermatológica. Esta es causada por extravasación, que consiste en daño tisular producto de la infiltración, por vía endovenosa, de los agentes quimioterápicos a los tejidos circundantes del sitio de punción. Lo anterior, requiere una actuación profesional rápida y eficaz para evitar resultados desfavorables para la persona. Objetivo: Comprender la percepción de profesionales de enfermería sobre el cuidado relacionado con la extravasación de fármacos antineoplásicos. Método: Se trata de un estudio de campo descriptivo-exploratorio con abordaje cualitativo, realizado con quince personas enfermeras que actúan en las salas de oncología de población adulta y ambulatoria de un hospital filantrópico ubicado en Recife/Pernambuco, Brasil. Los datos fueron recolectados entre enero y diciembre de 2020, a través de entrevistas y fueron sometidos a análisis de contenido por categorías temáticas. Resultados: Emergieron dos categorías: atención preventiva (desde la identificación de factores de riesgo hasta la educación de la persona y del equipo de salud) y atención directa (desde la identificación de la ocurrencia hasta la gestión institucional del evento). Conclusión: Se entendió que la percepción de la persona profesional de enfermería destaca la importancia de la planificación del cuidado, incluyendo la intervención inmediata, el registro de eventos y el seguimiento después de la extravasación, como forma de realizar cuidados especializados y con mayor seguridad.

Introduction: The use of antineoplastic chemotherapies acting at the cellular level with the aim of treating malignant neoplasms can lead to the emergence of dermatological toxicity caused by extravasation. This toxicity consists of tissue damage resulting from the infiltration, by intravenous route, of the chemotherapeutic agents to the surrounding tissues, requiring quick and effective professional action to avoid unfavorable outcomes for the patient. Objective: To understand the nurses' perception of care related to extravasation of antineoplastic drugs. Method: This is a descriptive-exploratory field study with a qualitative approach; it was carried out with fifteen nurses who work in the outpatient and adult oncology wards of a philanthropic hospital located in Recife/Pernambuco, Brazil. Data were collected between January and December 2020 through interviews and underwent thematic-category content analysis. Results: Two categories emerged: Preventive Care: from the identification of risk factors to the patient and health team education; and Direct Care: from the identification of the occurrence to the institutional management of the event. Conclusion: It was understood that the nurse's perception highlights the importance of care planning, including immediate intervention, event registration, and patient follow-up after extravasation, to perform specialized care and with greater safety.

Manejo de reações adversas dermatológicas em pacientes submetidos à terapia quimioterápica antineoplásica / Management of dermatological adverse reactions in patients undergoing antineoplastic chemotherapy

Objetivo: o presente estudo tem como objetivo reunir recomendações de cuidados considerando a prevenção e tratamento de lesões de pele induzidas pelo tratamento com quimioterápicos antineoplásicos, de acordo com os estudos e consensos atuais. Metodologia: realizou-se um estudo bibliográfico para levantamento das relações entre os principais fármacos antineoplásicos e suas intercorrências dermatológicas, bem como seus respectivos manejos, para subsidiar a orientação e aconselhamento aos profissionais de saúde que acompanham o paciente oncológico. Resultado: os principais problemas dermatológicos decorrentes do uso de antineoplásicos correspondem às lesões de pele, tais como a descoloração, hiperpigmentação, fotossensibilidade, eritemas, descamação e prurido. Também são recorrentes os efeitos adversos que acometem os pelos e cabelos, resultando em alopecia, e a modificação do crescimento e lesões nas unhas. Tratamentos específicos para cada caso são capazes de amenizar ou reverter os problemas. Conclusão: as reações adversas aos medicamentos envolvendo quimioterapia são frequentes na prática oncológica, e variam em termos de frequência e gravidade, atingindo diversos anexos cutâneos. O adequado manejo destes efeitos melhora a integridade da pele e demais estruturas, proporcionando a esses pacientes a melhoria da autoestima e da qualidade de vida.

Objective: the present study aims to gather care recommendations considering the prevention and treatment of skin lesions induced by treatment with antineoplastic chemotherapy, according to current studies and consensus. Methodology: a bibliographical study was carried out to survey the relationships between the main antineoplastic drugs and their dermatological intercurrences, as well as their respective management, to subsidize the guidance and counselling of health professionals who treat cancer patients. Result: the main dermatological problems arising from the use of antineoplastic agents correspond to skin lesions, such as discoloration, hyperpigmentation, photosensitivity, erythema, scaling and pruritus. Adverse effects that affect hair and body hair are also recurrent, resulting in alopecia, and the modification of growth and lesions on the nails. Specific treatments for each case can alleviate or reverse the problems. Conclusion: adverse drug reactions involving chemotherapy are frequent in oncology practice, and vary in terms of frequency and severity, affecting various skin appendages. Proper management of these effects improves the integrity of the skin and other structures, providing these patients with improved self-esteem and quality of life.

Chemotherapy and Anticancer Drugs Adjustment in Obesity: A Narrative Review.

BACKGROUND: Obese individuals have higher rates of cancer incidence and cancer- related mortality. The worse chemotherapy outcomes observed in this subset of patients are multifactorial, including the altered physiology in obesity and its impact on pharmacokinetics, the possible increased risk of underdosing, and treatment-related toxicity. AIMS: The present review aimed to discuss recent data on physiology, providing just an overall perspective and pharmacokinetic alterations in obesity concerning chemotherapy. We also reviewed the controversies of dosing adjustment strategies in adult and pediatric patients, mainly addressing the use of actual total body weight and ideal body weight. METHODS: This narrative review tried to provide the best evidence to support antineoplastic drug dosing strategies in children, adolescents, and adults. RESULTS: Cardiovascular, hepatic, and renal alterations of obesity can affect the distribution, metabolism, and clearance of drugs. Anticancer drugs have a narrow therapeutic range, and variations in dosing may result in either toxicity or underdosing. Obese patients are underrepresented in clinical trials that focus on determining recommendations for chemotherapy dosing and administration in clinical practice. After considering associated comorbidities, the guidelines recommend that chemotherapy should be dosed according to body surface area (BSA) calculated with actual total body weight, not an estimate or ideal weight, especially when the intention of therapy is the cure. CONCLUSION: The actual total body weight dosing appears to be a better approach to dosing anticancer drugs in both adults and children when aiming for curative results, showing no difference in toxicity and no limitation in treatment outcomes compared to adjusted doses.

Elaboração e implantação de protocolo de infiltração e extravasamento de antineoplásicos em acesso venoso central / Elaboración e implementación de un protocolo para la infiltración y extravación de antineoplásicos en el acceso venoso central / Elaboration and implementation of a protocol for infiltration and extravassion of antineoplastics in central venous access

Objetivo: Relatar a experiência na elaboração e implantação do protocolo de extravasamento e infiltração de antineoplásicos em acesso venoso central. Método: estudo descritivo, tipo relato de experiência realizado de fevereiro a maio de 2021. Resultados: Após a busca de evidências na literatura, foi elaborado um fluxograma referente aos cuidados de enfermagem realizados durante e após o extravasamento/infiltração. Além das medidas iniciais padronizou-se o uso da hialuronidase tópica e da fotobiomodulação (1 a 3 joules, com potência de 100 miliwats). A área deveria ser demarcada e se possível fotografada. Após a validação do protocolo por um grupo de enfermeiros especialistas e pelo escritório de qualidade, foi implantado em um Ambulatório de Oncologia de Hospital Público do interior do Estado de São Paulo. Conclusão: Apesar de raro, o extravasamento em acesso central pode acontecer e a equipe precisa de um protocolo assistencial para padronizar a conduta e garantir o sucesso da terapêutica.(AU)

Objective: To report the experience in the elaboration and implementation of the protocol for extravasation and infiltration of anticancer drugs in central venous access. Method: descriptive study, experience report type carried out from February to May 2021. Results: After searching for evidence in the literature, a flowchart was created referring to the nursing care performed during and after the extravasation/infiltration. In addition to the initial measurements, the use of topical hyaluronidase and photobiomodulation (1 to 3 joules, with a potency of 100 milliwatts) was standardized. The area should be demarcated and, if possible, photographed. After validation of the protocol by a group of specialist nurses and by the quality office, it was implemented in an Oncology Outpatient Clinic of a Public Hospital in the interior of the State of São Paulo. Conclusion: Although rare, extravasation in central access can happen and the team needs a care protocol to standardize the conduct and ensure the success of the therapy.(AU)

Objetivo: Informar la experiencia en la elaboración e implementación del protocolo de extravasación e infiltración de fármacos antineoplásicos en acceso venoso central. Método: estudio descriptivo, tipo relato de experiencia realizado de febrero a mayo de 2021. Resultados: Después de la búsqueda de evidencias en la literatura, se elaboró un diagrama de flujo sobre los cuidados de enfermería realizados durante y después de la extravasación/infiltración. Además de las mediciones iniciales, se estandarizó el uso de hialuronidasa tópica y fotobiomodulación (1 a 3 julios, con una potencia de 100 milivatios). El área debe ser delimitada y, si es posible, fotografiada. Después de la validación del protocolo por un grupo de enfermeros especialistas y por la oficina de calidad, fue implantado en un Ambulatorio de Oncología de un Hospital Público del interior del Estado de São Paulo. Conclusión: aunque rara, la extravasación en el acceso central puede ocurrir y el equipo necesita un protocolo de atención para estandarizar la conducta y garantizar el éxito de la terapia.(AU)

Efeitos da judicialização de medicamentos antineoplásicos nos serviços farmacêuticos em oncologia / Judicialization effects of antineoplastic drugs in a public cancer care facility / Efectos de la judicialización de los fármacos antineoplásicos en un servicio público de atención oncológica

Objetivo: analisar como os efeitos das demandas judiciais quanto aos aspectos regulatório, técnico, logístico e clínico impactam os serviços farmacêuticos em oncologia. Metodologia: estudo descritivo e exploratório, utilizando dados de processos judiciais recebidos pelo Instituto Nacional do Câncer (INCA), entre janeiro de 2009 e dezembro de 2018, e que resultaram no fornecimento de antineoplásicos. As variáveis foram analisadas nas dimensões médico-sanitária e político-administrativa, e correlacionadas aos seus efeitos nos serviços farmacêuticos em oncologia, nas perspectivas regulatória, logística, técnica e clínica. Resultados: foram identificados 41 processos judiciais que demandaram 14 antineoplásicos diferentes no período. Todos os medicamentos possuíam registro válido na Agência Nacional de Vigilância Sanitária; os anticorpos monoclonais foram os mais demandados; e o gasto total no período ultrapassou R$ 3 milhões. O descumprimento de aspectos normativos; as implicações técnicas e logísticas para preparo de antineoplásicos adquiridos pelos pacientes com recursos advindos de demandas judiciais; e a insuficiência de evidências científicas que suportem a adequada tomada de decisão foram alguns dos efeitos da judicialização para os serviços farmacêuticos em oncologia. Conclusão: os resultados permitiram ampliar o debate sobre os efeitos da judicialização da saúde, considerando aspectos basilares da assistência farmacêutica imbricados na rotina dos serviços de saúde.

Objective: to analyze the effects of lawsuits regarding the regulatory, technical, logistical and clinical aspects that impact the pharmaceutical services. Methods: descriptive and exploratory study using data from lawsuits received by a reference cancer care facility between January 2009 and December 2018, and which resulted in the supply of antineoplastic drugs. The variables were analyzed in the clinical-sanitary and regulatory-institutional dimensions and correlated to its effects on pharmaceutical services in oncology, from regulatory, logistical, technical, and clinical perspectives. Results: a total of 41 lawsuits demanded 14 different antineoplastic drugs in the period. All medicines had a valid Brazilian National Health Surveillance Agency registration, monoclonal antibodies were the most demanded and the total expenditure in the period exceeded R$ 3 million. Non-compliance with normative aspects, technical and logistical implications for the preparation of antineoplastic drugs purchased by patients with resources from lawsuits and lack of scientific evidence to support adequate decision-making were discussed as some of the judicialization effects for pharmaceutical services. Conclusion: the results made it possible to broaden the debate on the effects of health judicialization considering the basic aspects of pharmaceutical care imbricated in the routine of health services.

Objetivo: analizar los efectos de los juicios sobre los aspectos regulatorios, técnicos, logísticos y clínicos que impactan los servicios farmacéuticos. Metodología: estudio descriptivo y exploratorio con datos de los juicios recibidos por un centro oncológico de referencia entre enero de 2009 y diciembre de 2018 y que resultaron en el suministro de fármacos antineoplásicos. Las variables fueron analizadas en las dimensiones médico-sanitaria y político-administrativa, y correlacionado con sus efectos sobre los servicios farmacéuticos en oncología, desde las perspectivas regulatoria, logística, técnica y clínica. Resultados: un total de 41 demandas demandaron 14 antineoplásicos diferentes en el período. Todos los medicamentos tenían un registro válido de la Agencia Nacional de Vigilancia Sanitaria de Brasil, los anticuerpos monoclonales fueron los más demandados y el gasto total en el período superó los R$ 3 millones. El incumplimiento de aspectos normativos, las implicaciones técnicas y logísticas para la preparación de fármacos antineoplásicos adquiridos por pacientes con recursos de litigios y la falta de evidencia científica que sustente una adecuada toma de decisiones se discutieron como algunos de los efectos de judicialización para los servicios farmacéuticos. Conclusión: los resultados permitieron ampliar el debate sobre los efectos de la judicialización de la salud, considerando los aspectos básicos de la atención farmacéutica imbricados en la rutina de los servicios de salud.

Cutaneous adverse events to systemic antineoplastic therapies: a retrospective study in a public oncologic hospital

Abstract Background: Mucocutaneous adverse events are common during anticancer treatment, with variable consequences for the patient and their therapeutic regimen. Objective: To evaluate the most common adverse events, as well as the drugs associated with their appearance and the consequences for cancer treatment. Methods: A retrospective study was carried out through the analysis of patients treated at the Clinical Dermatology Unit of a public oncologic hospital. Results: A total of 138 patients with 200 adverse events were evaluated. The most commonly identified adverse events were nail and periungual changes (20%), papulopustular eruptions (13%), acneiform eruptions (12%), hand-foot syndrome (6.5%), hand-foot skin reaction (6%), and xerosis (6%). The most frequently associated antineoplastic treatment groups were classical chemotherapy (46.2%), target therapy (32.3%), and other non-antineoplastic drugs used in neoplasia protocols (16.5%). Of the total number of patients, 17.4% had their treatment suspended or changed due to a dermatological adverse event. Study limitations: Retrospective study and analysis of patients who were referred for specialized dermatological examination only, not allowing the assessment of the actual incidence of adverse events. Conclusion: A wide variety of dermatological manifestations are secondary to antineoplastic treatment with several different drugs resulting, not rarely, in the interruption or modification of therapeutic regimens.

Cutaneous adverse events to systemic antineoplastic therapies: a retrospective study in a public oncologic hospital.

BACKGROUND: Mucocutaneous adverse events are common during anticancer treatment, with variable consequences for the patient and their therapeutic regimen. OBJECTIVE: To evaluate the most common adverse events, as well as the drugs associated with their appearance and the consequences for cancer treatment. METHODS: A retrospective study was carried out through the analysis of patients treated at the Clinical Dermatology Unit of a public oncologic hospital. RESULTS: A total of 138 patients with 200 adverse events were evaluated. The most commonly identified adverse events were nail and periungual changes (20%), papulopustular eruptions (13%), acneiform eruptions (12%), hand-foot syndrome (6.5%), hand-foot skin reaction (6%), and xerosis (6%). The most frequently associated antineoplastic treatment groups were classical chemotherapy (46.2%), target therapy (32.3%), and other non-antineoplastic drugs used in neoplasia protocols (16.5%). Of the total number of patients, 17.4% had their treatment suspended or changed due to a dermatological adverse event. STUDY LIMITATIONS: Retrospective study and analysis of patients who were referred for specialized dermatological examination only, not allowing the assessment of the actual incidence of adverse events. CONCLUSION: A wide variety of dermatological manifestations are secondary to antineoplastic treatment with several different drugs resulting, not rarely, in the interruption or modification of therapeutic regimens.

Analysis of the interventions in antineoplastic therapy by a clinical pharmacy service at a tertiary hospital in Brazil.

BACKGROUND: Medication errors are avoidable occurrences that can assume clinically significant dimensions and impose relevant costs to the health system, especially in the context of antineoplastic therapy. OBJECTIVE: Assess the clinical significance and economic impacts of a clinical pharmaceutical service. This retrospective study consists of an analysis of pharmacy interventions and drug-related problems found in a review of electronic prescriptions referring to antineoplastic therapy of a public teaching tertiary hospital in Brazil. METHOD: Retrospective descriptive study obtained from electronic records of drug-related problems and pharmaceutical interventions related to antineoplastic therapy for oncological and hematological diseases, obtained through the pharmacotherapy review service. The accepted interventions were analyzed for the financial impact generated, evaluating your direct costs. The perception of clinical significance of a random sample of interventions was ascertained by the experts' opinion, using the Delphi method. RESULTS: The most frequent problem was a "lack of information to professionals" (25.06%), "problems as to the frequency and interval of doses" (22.90%), and "medication underdosing" (16.20%). Dose adjustment (31.50%) and clarifications (30.90%) were the most frequent pharmaceutical interventions. In the second round of Delphi, experts rated 77.77% of interventions as extremely significant and very significant. The main drugs reported in the interventions were cyclophosphamide, carboplatin, methotrexate, folinic acid, and monoclonal antibodies. The savings amounted to US$1,193,970.18 and involved mainly bortezomib, dactinomycin, and monoclonal antibodies. CONCLUSION: Clinical pharmacy services contributed to the rational use of medicines presenting clinical significance and avoiding waste of financial resources.

Adherence to thalidomide in patients with multiple myeloma: A cross-sectional study in a Brazilian metropolis.

PURPOSE: The treatment of multiple myeloma (MM) has advanced with the introduction of immunomodulators (IMiDS). Thalidomide is the IMiD available in Brazil with free access to MM patients. Adherence to treatment with IMiDs is essential for a successful therapy. The study proposed to describe adherence to thalidomide treatment in patients diagnosed with MM in onco-hematological outpatient clinics. METHODS: This is a cross-sectional study with patients over 18 years of age diagnosed with MM undergoing thalidomide treatment. Adherence was measured by the Proportion of Days Covered (PDC), which is an indirect method of measuring adherence that uses database-related medication dispensing information. Patients with PDC ≥90 were classified as adherent. The association between adherence and independent variables was assessed in univariate and multivariate analyses using logistic regression. RESULTS: A total of 65 patients with a median age of 62.6 years were identified. The median PDC was 93.7%. The frequency of adherence to thalidomide was 56.9%. Adherence to thalidomide showed a negative association with hospitalization in the last 12 months (OR = 0.202; 95% CI = 0.060-0.687) and with higher schooling (OR =0.161; 95% CI = 0.039-0.667) and a positive association with higher income (OR = 5.115; 95% CI = 1.363-19.190). CONCLUSION: Most patients from onco-hematological outpatient clinics in a metropolitan region of southeastern Brazil showed high adherence to thalidomide, which was independently associated with higher income, hospitalization, and higher schooling. More studies are required to understand better the determinants of adherence to thalidomide in the country.

Melitina: o uso do principal componente da peçonha de abelha no combate de linhagens de células tumorais pulmonares / Melittin: the use of the main component of bee venom in the fight against lung tumor cell lines

Introdução: Melitina é um peptídeo formado por 26 aminoácidos e principal composto da peçonha produzida por abelhas do gênero Apis. Estudos pré-clínicos têm demonstrado uma capacidade antineoplásica do composto, evidenciando seu efeito sobre linhagens celulares de câncer. O câncer de pulmão é o câncer que mais mata no mundo, sendo que 90% dos casos da doença estão relacionados a um histórico tabagista. O diagnóstico tardio muitas vezes devido à falta de sintomas clínicos compromete diretamente o tratamento e o prognóstico, gerando uma baixa taxa de sobrevida. Neste sentido, a melitina surge como uma abordagem no tratamento de câncer de pulmão. Objetivo: Realizar uma revisão integrativa da literatura sobre as pesquisas publicadas nos últimos cinco anos sobre o efeito da melitina em linhagens de células tumorais pulmonares humanas. Resultados: Foram encontradas 15 publicações, 10 foram excluídas por não responderem diretamente ao objetivo proposto ou por se tratarem de artigos duplicados e cinco foram escolhidas para compor esta revisão. Discussão: Os artigos avaliados relatam o efeito anticancerígeno da melitina sobre linhagens celulares de câncer de pulmão in vitro e in vivo. Conclusão: Devido sua atividade citotóxica a melitina é uma candidata no desenvolvimento de novos tratamentos de câncer.

Introduction: Melittin is a peptide formed by 26 amino acids and the main compound of the venom produced by honeybees. Preclinical studies demonstrated an antineoplastic capacity of the compound, evidencing its effect on cancer cell lines. Lung cancer is the deadliest cancer in the world, nine out of ten cases of this disease are related to smoking history. Late diagnosis, often due to lack of clinical symptoms, directly compromises treatment and prognosis, generating a low survival rate. In this sense, melittin appears as a therapeutic approach in lung cancer treatment. Objective: Carry out an integrative review of the literature on research published in the last five years about the effect of melittin on human lung tumor cell lines. Results: 15 publications were found, 10 were excluded because they didn't respond directly to the proposed objective or because they were duplicate articles, and five were chosen to compose this review. Discussion: Melittin proved to be efficient in controlling lung tumor cell lines, corroborating the results already reported in other tumor cell lines. Conclusion: The use of melittin is a potential approach in the treatment of lung cancer.

How can the dental surgeon promote oral health in patients submitted to chemotherapy? / Como o cirurgião dentista pode promover saúde bucal em pacientes submetidos à quimioterapia?

Lesions that affect the oral cavity resulting from chemotherapy can lead to systemic impairment, increasing the length of hospital stay, impairing the patient's quality of life. Through a integrative review, this work aims to show the conduct and importance of dentists in promoting oral health and preventing an oral infectious focus. The search was performed in the Pubmed, Cochrone, SciElo and Virtual Health Library (VHL) databases, using the descriptors in English, oral care and Chemotherapy and Cancer treatment and dentistry, filtering only articles in English and published between 2006 and 2021. The search located six hundred and twenty articles, but only seven met the search criteria. One author used a mouthwash containing propolis where 65% of patients were cured on the seventh day after the onset of oral mucositis (OM) lesions. One author used cryotherapy with chamomile infusion, patients who underwent this approach did not pass grade I, being effective in reducing the occurrence of OM, and the other two authors proposed a protocol for oral cavity care. All authors obtained satisfactory results.(AU)

As lesões que acometem a cavidade oral decorrente ao tratamento quimioterápico podem levar a um comprometimento sistêmico aumentando o tempo de internação hospitalar, prejudicando a qualidade de vida do paciente. O foco principal do cirurgião-dentista é identificar e remover fontes de infecção na cavidade oral antes do início da quimioterapia, controlar as possíveis lesões durante o tratamento. Após o tratamento quimioterápico, o paciente retornará para os cuidados dentários gerais, proporcionando manutenção da saúde bucal e prevenção de complicações ao longo prazo do tratamento do câncer. Através de uma revisão integrativa o objetivo desse trabalho é mostrar a conduta e a importância do cirurgião-dentista para promover saúde bucal e prevenir um foco infeccioso oral. A busca foi realizada nas bases de dados Pubmed, Cochrone, SciElo e Biblioteca virtual em saúde (BVS), foram utilizados os descritores em inglês, oral care and Chemotherapy and Cancer treatment and dentistry, filtrando somente os artigos na língua inglesa, estudos com seres humanos e os artigos publicados no intervalo de 2006-2021. A busca com os descritores citados encontrou seiscentos e vinte artigos, entretanto somente sete estavam dentro dos critérios da pesquisa. Um autor utilizou bochecho de própolis, outro crioterapia com infusão de camomila e os outros dois propuseram protocolo de cuidados com a cavidade oral. Todos os autores obtiveram resultados satisfatórios. (AU)

Knowledge about antineoplastic drugs: implications for the health of nursing workers in a general hospital / Conocimientos acerca de las drogas antineoplásicas: implicaciones a la salud del trabajador de enfermería en hospital general / Conhecimentos sobre drogas antineoplásicas: implicações para a saúde do trabalhador de enfermagem em hospital geral

ABSTRACT Objectives: to understand, from a worker's health perspective, the knowledge of nursing professionals about the use of antineoplastic drugs in a general hospital. Methods: a descriptive and exploratory study with a qualitative approach. It was conducted at a university hospital, between April and August 2018, with 35 nursing professionals who responded to a semi-structured interview. Thematic analysis was used for data treatment. Results: from the data, three thematic categories emerged, related to the nursing professionals' knowledge about antineoplastic drugs and their effects on workers' health; situations in which exposure to these drugs occurs; and protection mechanisms for the patient, the environment, and the worker. Final Considerations: the nursing professionals had little knowledge about antineoplastic drugs. The practices related to handling and the necessary protective measures to deal with these drugs were empirically determined and relatively subsidized the knowledge acquired by the professionals.

RESUMEN Objetivos: comprender, en la perspectiva de salud del trabajador, los conocimientos de los profesionales de enfermería sobre la utilización de drogas antineoplásicas en un hospital general. Métodos: estudio descriptivo y exploratorio con abordaje cualitativo. Realizado en un hospital universitario, entre abril y agosto de 2018, con 35 profesionales de enfermería que respondieron una entrevista semiestructurada. Utilizado el análisis temático para el tratamiento de datos. Resultados: emergieron, de los datos, tres categorías temáticas relacionadas a conocimientos de los profesionales de enfermería sobre drogas antineoplásicas y sus efectos para la salud del trabajador; situaciones en que ocurre la exposición a esas drogas; y mecanismos de protección al paciente, medio ambiente y trabajador. Consideraciones Finales: los profesionales de enfermería presentaban poco conocimiento sobre las drogas antineoplásicas. Las prácticas relacionadas al manejo y medidas de protección necesarias para lidiar con esas drogas eran empíricamente determinadas y subsidiaban relativamente el conocimiento adquirido por los profesionales.

RESUMO Objetivos: compreender, na perspectiva da saúde do trabalhador, os conhecimentos dos profissionais de enfermagem sobre a utilização de drogas antineoplásicas em um hospital geral. Métodos: estudo descritivo e exploratório com abordagem qualitativa. Foi realizado em um hospital universitário, entre abril e agosto de 2018, com 35 profissionais de enfermagem que responderam a uma entrevista semiestruturada. Utilizou-se a análise temática para o tratamento dos dados. Resultados: emergiram, dos dados, três categorias temáticas relacionadas aos conhecimentos dos profissionais de enfermagem sobre drogas antineoplásicas e seus efeitos para a saúde do trabalhador; situações em que ocorre a exposição a essas drogas; e mecanismos de proteção ao paciente, ao meio ambiente e ao trabalhador. Considerações Finais: os profissionais de enfermagem apresentavam pouco conhecimento sobre as drogas antineoplásicas. As práticas relacionadas ao manuseio e as medidas de proteção necessárias para lidar com essas drogas eram empiricamente determinadas e subsidiavam relativamente o conhecimento adquirido pelos profissionais.

Adolescents' understanding of chemotherapy-related adverse events: a concept elicitation study / Compreensão dos adolescentes sobre eventos adversos relacionados à quimioterapia: um estudo de elicitação de conceitos / La comprensión de los adolescentes de los efectos adversos relacionados con la quimioterapia: un estudio de elicitación de conceptos

Abstract Objective: to document adolescents' understanding of chemotherapy-related core adverse events from the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events and thus begin the validation process of this tool's items with Brazilian adolescents. Method: this is a prospective, qualitative study of concept elicitation. The participants were 17 adolescents aged 13-18 years and undergoing chemotherapy in three hospitals in São Paulo - SP, Brazil. Cognitive interviews were conducted with questions based on chemotherapy-related adverse events. Data were analyzed for responsiveness and missingness. Results: adolescents could and were willing to provide descriptive information about their chemotherapy adverse events, including physical and emotional events. Some participants suggested alternative terms to name the adverse events and some used more complex terms, but most were satisfied with the primary terms used by the researchers. Conclusion: this study represents the first steps towards understanding how adolescent cancer patients identify, name, and describe these events by cognitive interviewing to help design future assessment instruments focused on this age group.

Resumo Objetivo: documentar a compreensão dos adolescentes sobre os principais eventos adversos relacionados à quimioterapia a partir da versão Pediátrica dos Desfechos Relatados pelo Paciente (Patient-Reported Outcomes) dos Critérios de Terminologia Comum para Eventos Adversos (Common Terminology Criteria for Adverse Events), e assim iniciar o processo de validação dos itens desta ferramenta com adolescentes brasileiros. Método: trata-se de um estudo prospectivo, qualitativo, de elicitação de conceitos. Participaram do estudo 17 adolescentes de 13 a 18 anos, submetidos à quimioterapia em três hospitais da cidade de São Paulo-SP, Brasil. Foram realizadas entrevistas cognitivas com perguntas baseadas em eventos adversos relacionados à quimioterapia. Os dados foram analisados quanto à responsividade e ausência de resposta. Resultados: os adolescentes puderam e estavam dispostos a fornecer informações descritivas sobre seus eventos adversos quimioterápicos, incluindo eventos físicos e emocionais. Alguns participantes sugeriram nomes alternativos para os eventos adversos e alguns usaram termos mais complexos, mas a maioria ficou satisfeita com aqueles utilizados pelos pesquisadores. Conclusão: este estudo representa os primeiros passos para entender como os adolescentes com câncer identificam, nomeiam e descrevem esses eventos por meio de entrevistas cognitivas para ajudar a criar futuros instrumentos de avaliação focados nessa faixa etária.

Resumen Objetivo: documentar la comprensión de los adolescentes de los principales eventos adversos relacionados con la quimioterapia a partir de la versión de los Criterios Terminológicos Comunes para Eventos Adversos reportados por los pacientes pediátricos y así iniciar el proceso de validación de los ítems de esta herramienta con adolescentes brasileños. Método: este es un estudio prospectivo y cualitativo de elicitación de conceptos. Los participantes fueron 17 adolescentes de entre 13 y 18 años de edad que recibían quimioterapia en tres hospitales de São Paulo-SP, Brasil. Se realizaron entrevistas cognitivas con preguntas basadas en eventos adversos relacionados con la quimioterapia. Los datos se analizaron en función de la presencia y ausencia de respuesta. Resultados: los adolescentes podían y estaban dispuestos a proporcionar información descriptiva sobre los efectos adversos de la quimioterapia, incluidos los físicos y emocionales. Algunos participantes sugirieron términos alternativos para denominar los eventos adversos y otros utilizaron términos más complejos, pero la mayoría se mostró satisfecha con los términos principales utilizados por los investigadores. Conclusión: este estudio representa los primeros pasos hacia la comprensión de cómo los pacientes adolescentes con cáncer identifican, nombran y describen estos eventos mediante entrevistas cognitivas para ayudar a diseñar futuros instrumentos de evaluación centrados en este grupo de edad.

Antineoplastics Encapsulated in Nanostructured Lipid Carriers.

Ideally, antineoplastic treatment aims to selectively eradicate cancer cells without causing systemic toxicity. A great number of antineoplastic agents (AAs) are available nowadays, with well-defined therapeutic protocols. The poor bioavailability, non-selective action, high systemic toxicity, and lack of effectiveness of most AAs have stimulated the search for novel chemotherapy protocols, including technological approaches that provide drug delivery systems (DDS) for gold standard medicines. Nanostructured lipid carriers (NLC) are DDS that contain a core of solid and lipid liquids stabilised by surfactants. NLC have high upload capacity for lipophilic drugs, such as the majority of AAs. These nanoparticles can be prepared with a diversity of biocompatible (synthetic or natural) lipid blends, administered by different routes and functionalised for targeting purposes. This review focused on the research carried out from 2000 to now, regarding NLC formulations for AAs (antimetabolites, antimitotics, alkylating agents, and antibiotics) encapsulation, with special emphasis on studies carried out in vivo. NLC systems for codelivery of AAs were also considered, as well as those for non-classical drugs and therapies (natural products and photosensitisers). NLC have emerged as powerful DDS to improve the bioavailability, targeting and efficacy of antineoplastics, while decreasing their toxic effect in the treatment of different types of cancer.

Protocolo de desensibilización rápida en pacientes con reacción moderada a severa de hipersensibilidad a citostáticos / Rapid desensitization protocol in patients with moderate to severe hypersensitivity reaction to cytostatics

Introducción: La desensibilización rápida a medicamentos induce una tolerancia temporal a los quimioterapéuticos que provocan reacciones de hipersensibilidad. Objetivo: Evaluar el protocolo de desensibilización rápida en escenario ambulatorio en pacientes que presentaron reacciones de hipersensibilidad a fármacos citotóxicos. Métodos: Se realizó un estudio observacional, y retrospectivo, de 30 pacientes con cáncer que desarrollaron reacciones de hipersensibilidad entre los años 2016 y 2018, tratados en el Hospital de Día del Servicio de Oncología del Clínico Quirúrgico Hermanos Ameijeiras. Se clasificaron según su intensidad, y se analizaron variables demográficas, características clínicas, y síntomas presentados. Se utilizó un protocolo en doce etapas basado en tres diluciones del fármaco. Se administró premedicación en todos los casos. Se realizó estadística descriptiva, y para la asociación entre variables, se utilizó la prueba estadística Chi-cuadrado. Resultados: La mediana de edad fue 54 años (23;77). Predominaron las mujeres; los menores de 60 años; tumor primario de colon; antecedentes de alergia; el oxaliplatino como fármaco más implicado; las RHS durante la infusión; e intensidad moderada. Fueron más frecuentes los síntomas cutáneos y gastrointestinales. Con la aplicación del protocolo se completó la quimioterapia planificada a los 30 pacientes (145 ciclos adicionales). Solo se presentaron ocho desensibilizaciones con reacciones leves de tipo cutáneas. El 94,5 por ciento de las desensibilizaciones no presentaron reacción alguna. Conclusiones: Constituye el primer reporte nacional de la utilización exitosa de un protocolo de desensibilización rápida a citostáticos que demostró ser eficaz y seguro en el escenario ambulatorio, con un manejo multidisciplinario(AU)

Introduction: Rapid desensitization to drugs induces a temporary tolerance to chemotherapeutics causing hypersensitivity reactions. Objective: To evaluate the rapid desensitization protocol in an outpatient setting in patients who had hypersensitivity reactions to cytotoxic drugs. Methods: An observational and retrospective study was carried out in 30 cancer patients, who developed hypersensitivity reactions, from 2016 to 2018. They were treated in the outpatient Oncology service at Hermanos Ameijeiras Surgical Clinical Hospital. These subjects were classified according to intensity; demographic variables, clinical characteristics, and symptoms were analyzed. A twelve-step protocol based on three dilutions of the drug was used. Premedication was administered in all cases. Descriptive statistics and for the association between variables were performed. Chi-square statistical test was used. Results: The median age was 54 years (23; 77). Predominance was observed in women, those under 60 years of age, primary colon tumor, history of allergy, oxaliplatin as the drug most implicated, HRH during infusion, and moderate intensity. Skin and gastrointestinal symptoms were more frequent. The planned chemotherapy was completed with the application of the protocol, in all 30 patients (145 additional cycles). There were only eight desensitization with mild skin-type reactions. 94.5 percent of desensitizations did not show any reaction. Conclusions: It constitutes the first national report of successful use of a rapid desensitization protocol to cytostatics that proved to be effective and safe in the outpatient setting with multidisciplinary management(AU)

Avaliação de interações medicamentosas potenciais em pacientes oncopediátricos internados / Evaluation of potential drug interactions in hospitalized pediatric oncology patients

O câncer é uma doença caracterizada pelo crescimento desordenado de células com capacidade de invadir tecidos adjacentes. Na oncologia pediátrica, as interações ocorrem principalmente com medicamentos de suporte prescritos durante o tratamento. Com isso, o presente estudo realizou a revisão da farmacoterapia para identificar e avaliar as interações medicamentosas potenciais (IMP) em pacientes oncopediátricos internados em um hospital público. Analisou-se 203 prescrições de 47 pacientes. Foi identificado 55 IMP no total, sendo 14 IMP diferentes e 1,2 IMP por paciente. A mais prevalente em 47,2% do total (n = 26) foi entre metotrexato e cotrimoxazol. Identificou-se 21 tipos de neoplasias, sendo a mais frequente a leucemia linfoblástica aguda (LLA). A correlação de Spearman foi + 0,71 (p < 0,001), indicando uma forte correlação entre a ocorrência de interações medicamentosas com número de medicamentos prescritos. Na análise de regressão logística multivariada os resultados demonstraram que apresentar LLA e polifarmácia foram os principais fatores associados para ocorrência de IMP. Destaca-se a probabilidade de ocorrência de IMP aumentar 9,7 vezes em pacientes polimedicados IC95% = 4,6-21,4 (p = 0,001) e OR em 12,1; IC95% = 5,8-26,9 em pacientes com LLA comparando os que não apresentam LLA (p = 0,001). Nessa perspectiva, os dados obtidos possibilitam fornecer subsídios para a implementação de estratégias de monitoramento das IMP, bem como de intervenções clínicas que garantam uma terapêutica mais eficaz contribuindo para a segurança dos pacientes oncopediátricos.

Cancer is a disease characterized by the disordered growth of cells capable of invading adjacent tissues. In pediatric oncology, drug-drug interactions occur mainly with supportive drugs prescribed during treatment. Thus, the present study aims to identify and evaluate the potential drug-drug interactions (PDDIs) in hospitalized pediatric oncology patients. 203 prescriptions of 47 patients were analyzed. A total of 55 PDDIs were identified, with 14 different PDDIs, and 1.2 PDDI per patient. The most prevalent 47.2% (n = 26) was methotrexate and cotrimoxazole. 21 types of neoplasms were identified, the most frequent being acute lymphoblastic leukemia (ALL). The Spearman correlation was +0.71 (p<0.001), indicating a strong correlation with the occurrence of potential drug-drug interactions and the number of drugs prescribed. In the multivariate logistic regression analysis, the results showed that having ALL and polypharmacy were the main associated factors for the occurrence of PDDI. The probability of the occurrence of PDDIs increases by 9.7 times in polymedicated patients (95%CI = 4.6-21.4 (p=0.001)) and 12.1 times in ALL patients compared to those without ALL (95% CI=5.8-26.9 (p = 0.001)). In this perspective, the data obtained make it possible to provide subsidies for the implementation of strategies to monitor and provide clinical interventions that guarantee a more effective treatment, contributing to the safety of pediatric oncology patients.

Retinol palmitate against toxicogenic damages of antineoplastic drugs on normal and tumor cells.

The lack of tissue selectivity of anticancer drugs generates intense collateral and adverse effects of cancer patients, making the incorporation of vitamins or micronutrients into the diet of individuals to reduce side or adverse effects of antineoplastics. The study aimed to evaluate the effects of retinol palmitate (RP) on the toxicogenic damages induced by cyclophosphamide (CPA), doxorubicin (DOX) and its association with the AC protocol (CPA + DOX), in Sarcoma 180 (S-180) tumor cell line, using the micronuclei test with a block of cytokinesis (CBMN); and in non-tumor cells derived from Mus musculus using the comet assay. The results suggest that CPA, DOX and AC protocol induced significant toxicogenic damages (P < 0.05) on the S-180 cells by induction of micronuclei, cytoplasmic bridges, nuclear buds, apoptosis, and cell necrosis, proving their antitumor effects, and significant damage (P < 0.001) to the genetic material of peripheral blood cells of healthy mice, proving the genotoxic potential of these drugs. However, RP modulated the toxicogenic effects of antineoplastic tested both in the CBMN test (P < 0.05), at the concentrations of 1, 10 and 100 IU/mL; as in the comet assay (P < 0.001) at the concentration of 100 IU/kg for the index and frequency of genotoxic damage. The accumulated results suggest that RP reduced the action of antineoplastics in non-tumor cells as well as the cytotoxic, mutagenic, and cell death in neoplastic cells.