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Breast and gynecological cancers are major health concerns due to their increasing incidence rates, and in some cases, their low survival probability. In recent years, multiple compounds of natural origin have been analyzed as alternative treatments for this disease. For instance, Acetogenins are plant secondary metabolites from the Annonaceae family, and its potential anticancer activity has been reported against a wide range of cancer cells both in vitro and in vivo. Several studies have demonstrated promising results of Acetogenins' antitumor capacity, given their selective activity of cellular inhibition at low concentrations. This review outlines the origin, structure, and antineoplastic activities in vitro and in vivo of Acetogenins from Annonaceae against breast cancer and gynecological cancers reported to date. Here, we also provide a systematic summary of the activity and possible mechanisms of action of Acetogenins against these types of cancer and provide references for developing future therapies based on Acetogenins and nanotechnologies.

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BACKGROUND: Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial. METHODS: We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of < 0.05 denoted statistically significant. RESULTS: 50,402 patients were included, of whom 778 (1,54%) took antipsychotic medication for at least 1 year. 1,086 (2,15%) with ovarian cancer and 49,316 (97,85%) with endometrial cancer. Antipsychotic use (OR 1.50; 1.06 to 2.13 95% CI; p-value 0.02), hypertension (OR 1.50; 95% CI 1.06 to 2.13; p-value < 0.01), nulliparity (OR 1.98; 95% CI 1.53 to 2.57; p-value < 0.01) and multiparity (OR 0.53; 95% CI 0.41 to 0.69; p-value < 0.01) showed significantly different distributions between groups of cancer and cancer-free patients. The primary endpoint of incidence risk of gynecological cancer by antipsychotic therapy showed a statistically significant difference (OR 1.67; 95% CI 1.02 to 2.73; p-value < 0.05) against the use of antipsychotic drugs. CONCLUSIONS: Our meta-analysis showed that the use of antipsychotic drugs increases the risk of gynecological cancers, particularly endometrial cancer. This result should be weighed against the potential effects of treatment for a balanced prescribing decision.

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Introdução: Pacientes com câncer apresentam uma tendência à perda ponderal e à desnutrição energético-proteica. Isso ocorre em razão das modificações que o organismo sofre pelo desenvolvimento da doença e pelos efeitos adversos do tratamento oncológico que contribuem para a redução da ingestão alimentar. Objetivo: Identificar evidências disponíveis na literatura científica sobre a ingestão alimentar de mulheres com tumores ginecológicos em tratamento oncológico. Método: Revisão integrativa da literatura cujas buscas foram realizadas nas bases de dados Embase, MEDLINE e LILACS por meio da associação de termos descritores e palavras livres. Foram incluídos nas análises estudos observacionais que avaliaram a ingestão alimentar de mulheres adultas com tumores ginecológicos durante o tratamento oncológico, redigidos em português, inglês e espanhol. Resultados: Esta revisão analisou seis estudos que investigaram a mudança na ingestão alimentar dessa população. Identificou-se uma redução da ingestão em até 31% de energia, 39,9% de proteínas, 33,7% de lipídeos, 28,7% de carboidratos e uma inadequação da ingestão de determinados micronutrientes. Conclusão: Mulheres com tumores ginecológicos durante o tratamento oncológico apresentam redução significativa da ingestão de energia, proteínas, lipídeos, carboidratos e micronutrientes. Considerando que a perda de peso e a desnutrição em pacientes com câncer está associada a desfechos clínicos negativos, a avaliação e a análise da ingestão alimentar desses indivíduos são fundamentais para possibilitar uma intervenção nutricional precoce, boa resposta ao tratamento e consequente melhoria da qualidade de vida

Introduction: Cancer patients tend to lose weight and energy-protein malnutrition because of the changes the organism undergoes caused by the progression of the disease and treatment-related adverse effects that contribute for the reduction of food intake. Objective: To identify scientific literature-based evidences on food intake of women with gynecological tumors undergoing cancer treatment. Method: Integrative literature review through searches at the Embase, MEDLINE and LILACS databases with the association of descriptive terms and free words. Observational studies in Portuguese, English and Spanish that evaluated the food intake of this population were included in the analyzes. Results: This review identified 6 studies that investigated the change in food intake of women with gynecological cancer undergoing cancer treatment. A reduction in intake was identified in until 31% of energy, 39.9% of proteins, 33.7% of lipids, 28.7% of carbohydrates and inadequate intake of certain micronutrients. Conclusion: Women with gynecological tumors during cancer treatment present significant reduction of energy, proteins, lipids, carbohydrates and micronutrients intake. Considering that weight loss and malnutrition in cancer patients are associated with negative clinical outcomes, the evaluation and analysis of the food intake of this population individuals is essential for early nutritional intervention, good response to treatment and improvement of the quality of life

Introducción: Los pacientes con cáncer tienen tendencia a la pérdida de peso y a la desnutrición calórico-proteica. Esto ocurre debido a los cambios que sufre el organismo debido al desarrollo de la enfermedad y los efectos adversos del tratamiento del cáncer que contribuyen a la reducción de la ingesta alimentaria. Objetivo: Identificar la evidencia disponible en la literatura científica sobre la ingesta alimentaria de mujeres con tumores ginecológicos en tratamiento oncológico. Método: Revisión integrativa de la literatura cuyas búsquedas se realizaron en las bases de datos Embase, MEDLINE y LILACS mediante la asociación de términos descriptivos y palabras libres. Se incluyeron en los análisis estudios observacionales que evaluaron la ingesta de alimentos de mujeres adultas con tumores ginecológicos durante el tratamiento del cáncer, escritos en portugués, inglés y español. Resultados: Esta revisión analizó seis estudios que investigaron el cambio en la ingesta de alimentos en esta población. Cuantificamos una reducción de la ingesta de hasta un 31% en energía, 39,9% en proteínas, 33,7% en lípidos, 28,7% en carbohidratos y una ingesta inadecuada de determinados micronutrientes. Conclusión: Las mujeres con tumores ginecológicos durante el tratamiento del cáncer tienen una reducción significativa en la ingesta de energía, proteínas, lípidos, carbohidratos y micronutrientes. Teniendo en cuenta que la pérdida de peso en pacientes con cáncer se asocia con resultados clínicos negativos, la evaluación de la ingesta alimentaria de estos individuos es fundamental para permitir una intervención nutricional precoz, una buena respuesta al tratamiento y la consecuente mejora de la calidad de vida

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BACKGROUND: Paclitaxel/carboplatin combination is the standard chemotherapeutic protocol for gynecologic cancers, but severe toxicities may compromise treatment. There is great inter-individual variability regarding the incidence and severity of toxicities, which may be due to single-nucleotide polymorphisms (SNPs) affecting drug disposition or cellular sensitivity. Here we investigate the impact of selected SNPs in ERCC1, ABCB1, CYP2C8, and CYP3A5 genes on the incidence of severe toxicities, including nephro- and hepatotoxicity. METHODS: A cohort of 507 gynecological cancer patients receiving paclitaxel/carboplatin was recruited at the Brazilian National Cancer Institute (INCA-Brazil). Clinical data were obtained during routine consultations or from electronic medical records. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). Genotyping was performed using real-time PCR. RESULTS: ABCB1 c.1236C>T was associated with moderate-to-severe (grades 2-4) nephrotoxicity (ORadjusted 2.40; 95% CI 1.39-4.15), even after adjustment for age (≥ 65) and diabetes. The risk association between ABCB1 c.1236C>T and moderate-to-severe nephrotoxicity following paclitaxel/carboplatin chemotherapy was also present among non-diabetic patients (ORadjusted 2.16; 95% CI 1.22-3.82). ERCC1 c.118C>T was the only individual variable associated with an increased risk for moderate-to-severe (grades 2-4) hepatotoxicity (OR 3.71; 95% CI 1.08-12.77), severe nausea (OR 4.18; 95% CI 1.59-10.95), and severe myalgia (OR 1.95; 95% CI 1.12-3.40). CONCLUSIONS: ABCB1 c.1236C>T and ERCC1 c.118C>T might serve as potential biomarkers for the risk of moderate-to-severe toxicities to carboplatin/paclitaxel chemotherapy of gynecological cancers.

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PURPOSE: Gynecologic malignancies are often detected in advanced stages, requiring chemotherapy with taxane/platinum combinations, which may cause severe toxicities, such as neutropenia and peripheral neuropathy. Gene polymorphisms are suspected as possible causes for the interindividual variability on chemotherapy toxicities. OBJECTIVE: To evaluate the role of ABCB1 1236C>T, 3435C>T; CYP2C8*3; CYP3A5*3C variants on paclitaxel/carboplatin toxicities. METHODS: A cohort of 503 gynecologic cancer patients treated with paclitaxel/carboplatin at the Brazilian National Cancer Institute (INCA-Brazil) was recruited (2013-2017). Polymorphisms were genotyped by real-time PCR, and toxicities were evaluated by patients' interviews at each chemotherapy cycle and by data collection from electronic records. The association of clinical features and genotypes with severe toxicities was estimated using Pearson's Chi square tests and multiple regression analyses, with calculation of adjusted odds ratios (ORadjusted), and respective 95% confidence intervals (95% CI). RESULTS: CYP2C8*3 was significantly associated with increased risks of severe (grades 3-4) neutropenia (ORadjusted 2.11; 95% CI 1.24-3.6; dominant model) and severe thrombocytopenia (ORadjusted 4.93; 95% CI 1.69-14.35; recessive model), whereas ABCB1 variant genotypes (ORadjusted 2.13; 95% CI 1.32-3.42), in association with CYP2C8*3 wild type (GG) (ORadjusted 1.93; 95% CI 1.17-3.19), were predictive of severe fatigue. CONCLUSIONS: The present study suggests that CYP2C8*3 is a potential predictor of hematological toxicities related to paclitaxel/carboplatin treatment. Since hematological toxicities, especially neutropenia, may lead to dose delay or treatment interruption, such prognostic evaluation may contribute to clinical management of selected patients with paclitaxel-based chemotherapy.

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O protocolo de paclitaxel e carboplatina (CARBO-TAX) é capaz de induzir reações adversas a medicamentos (RAM), comprometendo a qualidade de vida das pacientes. Este estudo teve como objetivo detectarsuspeitas de RAM (sRAM) relacionadas ao CARBO-TAX, em pacientes com câncer ginecológico, identificando os desdobramentos clínicos e o efeito da adesão à Terapia de Suporte (TS). Foi realizado estudo transversal descritivo em hospital oncológico, com pacientes submetidas ao CARBO-TAX. Os dados clínicos, laboratoriais, sociodemográficos, medicamentos utilizados e relatos de sRAM, foram coletados através de entrevista estruturada e análise de prontuário. Das 79 pacientes avaliadas, 39% relataram sRAM agudas e 100% sRAM tardia. Dentre as sRAM tardias, as prevalentes foram fadiga (68% - Grau 1 à 3) e náuseas (66% - Grau 1 à 2). Os principais desdobramentos clínicos foram busca à emergência (45%) e alteração da dose do CARBO-TAX (20%). A adesão a TS (78%) foi relacionada a redução significativa (p<0,05) nas sRAM de maior gravidade (Grau 3). Em conclusão, as sRAM associadas ao CARBO-TAX, afetam o plano terapêutico (alteração de dose/interrupção de protocolo) das pacientes e, a adesão a TS, reduz a gravidade da RAM, interferindo na qualidade e segurança da terapia antineoplásica.

The paclitaxel and carboplatin protocol (CARBO-TAX) is capable of inducing adverse drug reactions (ADR), compromising patients' quality of life. This study aimed to detect CARBO-TAX-related suspected ADRs (sADR) in patients with gynecological cancer, identifying clinical outcomes and the effect of adherence to Supportive Therapy (TS). A descriptive cross-sectional study was carried out in an oncology hospital, with patients submitted to CARBO-TAX. The clinical, laboratorial, sociodemographic data, medicines used and sADR reports were collected through a structured interview and chart analysis. Of the 79 patients evaluated, 39% reported acute sADR and 100% late sADR. Among the late sADR, the prevalent were fatigue (68% - Grade 1 to 3) and nausea (66% - Grade 1 to 2). The main clinical outcomes were the emergence (45%) and modification of the dose of CARBO-TAX (20%). The adherence to TS (78%) was related to a significant reduction (p <0.05) in the most serious sADR (Grade 3). In conclusion, the CARBO-TAX-associated sADR affect the therapeutic plan (dose change / protocol interruption) of patients, and adherence to TS reduces the severity of ADR, interfering with the quality and safety of antineoplastic therapy.

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INTRODUCTION: Venous thromboembolism (VTE) is a major complication of malignant diseases and is a frequent cause of death in patients with cancer. Managing anticoagulation in these patients is challenging because of the high risk of recurrent VTE and bleeding events. Rivaroxaban is an oral anticoagulant that provides rapid onset of anticoagulation. OBJECTIVE: The aim of this study was to describe the complications of rivaroxaban and potentially associated factors in patients with gynecologic cancer and VTE. METHODS: This was an observational study in women with gynecological cancer who developed VTE and were treated with 15 and 20 mg rivaroxaban at Instituto Nacional de Câncer from July 2014 to July 2015. RESULTS: Forty-one patients were treated with rivaroxaban. Most patients were younger than 60 years and presented cervical cancer; 58.5% of women did not have complications, thus remaining at a dose of 20 mg/d. Because of complications, 12.2% had the dose reduced to 15 mg/d, 12.2% had the drug suspended, 7.3% had progressive worsening of the disease with suspension of anticoagulation, and 9.8% progressed to death because of progression of the disease. CONCLUSIONS: Rivaroxaban has been documented as a low-cost, easily controlled option compared with standard therapy. Most participants in this study had no complications. However, it was not possible to assess associations with statistical significance. Further analytical studies with larger samples are required to evaluate the safety and efficacy of this treatment in patients with gynecologic cancer.

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The treatment of advanced gynecologic cancers remains palliative in most of cases. Although systemic treatment has entered into the era of targeted drugs the antitumor efficacies of current therapies are still limited. In this context there is a great need for more active treatment and rationally designed targeted therapies. The PI3K/AKT/mTOR is a signaling pathway in mammal cells that coordinates important cell activities. It has a critical function in the survival, growth, and proliferation of malignant cells and was object of important research in the last two decades. The mTOR pathway emerges as an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli and, through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Aberrant PI3K-dependent signaling occurs frequently in a wide range of tumor types, including endometrial, cervical, and ovarian cancers. The present study reviewed the available evidence regarding the potential impact of some mTOR pathway inhibitors in the treatment of gynecological cancer. Few advances in medical management have occurred in recent years in the treatment of advanced or recurrent gynecological malignancies, and a poor prognosis remains. Rationally designed molecularly targeted therapy is an emerging and important option in this setting; then more investigation in PI3K/AKT/mTOR pathway-targeted therapies is warranted.

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Objective: to describe the social, demographic and clinical profile, and functional capacity of women diagnosed with gynecological cancer, breast cancer and gestational trophoblastic disease during chemotherapy. Method: longitudinal retrospective study that evaluated the records of women treated in hospital clinics from January 2000 to December 2012. Results: they evaluated the records of 438 women. The analysis showed that were not able to perform their daily activities, limited to the activities of self-care. Older patients had greater functional impairment during therapy. Conclusions: the sample was women 41 to 50 years, diagnosed with breast cancer (50.9%) and made use of anthracycline based protocols (47%); the scores of the functional capacity of the sample fell from 78.22 to 73.57. It is evident that nursing care should focus on the control of signs and symptoms that impact the functional capacity of women under chemotherapy.

Objetivo: describir el perfil socio demográfico, clínico y capacidad funcional de mujeres diagnosticadas con cáncer ginecológico, mamario y enfermedad trofoblástica gestacional en tratamiento quimioterápico. Método: estudio longitudinal retrospectivo, que evaluó los registros de mujeres en tratamiento en un hospital de clínicas en el período de enero/2000-diciembre/2012. Resultados: fueron evaluados los registros de 438 mujeres. El análisis mostró que las pacientes no eran capaces de realizar sus actividades cotidianas, limitándose a las actividades del autocuidado. Las pacientes mayores sufrieron más comprometimiento funcional durante la terapéutica. Conclusiones: la muestra estudiada era de mujeres con 41-50 años, diagnosticadas con cáncer de mama (50,9%) y hacían uso de protocolos basados en antracíclicos (47%); los escores de la capacidad funcional de la muestra decayeron de 78,22 para 73,57. Se evidencia que los cuidados de enfermería deben centrarse en el control de señales y síntomas que causan impacto en la capacidad funcional de las mujeres en quimioterapia.

Objetivo: descrever o perfil sociodemográfico e clínico e a capacidade funcional de mulheres diagnosticadas com câncer ginecológico, câncer mamário e doença trofoblástica gestacional em tratamento quimioterápico. Método: estudo longitudinal retrospectivo, que avaliou os registros de mulheres em tratamento em um hospital de clínicas no período de janeiro de 2000 a dezembro de 2012. Resultados: foram avaliados os registros de 438 mulheres. A análise mostrou que as pacientes não eram capazes de realizar suas atividades cotidianas, limitando-se àquelas do autocuidado. As pacientes idosas sofreram maior comprometimento funcional durante a terapêutica. Conclusões: a amostra estudada era de mulheres com 41 a 50 anos, diagnosticadas com câncer de mama (50,9%), que faziam uso de protocolos baseados em antracíclicos (47%); os escores da capacidade funcional da amostra decaíram de 78,22 para 73,57. Evidencia-se que os cuidados de enfermagem devem centrar-se no controle de sinais e sintomas que causam impacto na capacidade funcional das mulheres sob quimioterapia.

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BACKGROUND: Most contraceptive methods present benefits beyond contraception; however, despite a large body of evidence, many healthcare professionals (HCPs), users and potential users are unaware of those benefits. This review evaluates the evidence for non-contraceptive benefits of hormonal and non-hormonal contraceptive methods. METHODS: We searched the medical publications in PubMed, POPLINE, CENTRAL, EMBASE and LILACS for relevant articles, on non-contraceptive benefits of the use of hormonal and intrauterine reversible contraceptive methods, which were published in English between 1980 and July 2014. Articles were identified using the following search terms: 'contraceptive methods', 'benefits', 'cancer', 'anaemia', 'heavy menstrual bleeding (HMB)', 'endometrial hyperplasia', 'endometriosis' and 'leiomyoma'. RESULTS: We identified, through the literature search, evidence that some combined oral contraceptives have benefits in controlling HMB and anaemia, reducing the rate of endometrial, ovarian and colorectal cancer and ectopic pregnancy as well as alleviating symptoms of premenstrual dysphoric disorder. Furthermore, the use of the levonorgestrel-releasing intrauterine system also controls HMB and anaemia and endometrial hyperplasia and cancer, reduces rates of endometrial polyps in users of tamoxifen and alleviates pain associated with endometriosis and adenomyosis. Depot medroxyprogesterone acetate controls crises of pain associated with sickle cell disease and endometriosis. Users of the etonogestrel-releasing contraceptive implant have the benefits of a reduction of pain associated with endometriosis, and users of the copper intrauterine device have reduced rates of endometrial and cervical cancer. CONCLUSIONS: Despite the high contraceptive effectiveness of many hormonal and intrauterine reversible contraceptive methods, many HCPs, users and potential users are concerned mainly about side effects and safety of both hormonal and non-hormonal contraceptive methods, and there is scarce information about the many benefits that these methods offer beyond contraception.

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