Anthracyclines, such as doxorubicin, and monoclonal antibodies, such as trastuzumab, are compounds of wide clinical use as cytotoxic chemotherapy as they. Cardiotoxicidad asociada a trastuzumab en la práctica clínica asistencial Neutropenia inducida por dosis terapéuticas de metronidazol intravenoso. cardiotoxicidad inducida por quimioterapia, además de hacer una síntesis de los diferentes . tion (anthracyclines, trastuzumab, tyrosine kinase inhibitors.
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Adverse reactions for the use of the monoclonal trastuzumab antibody in the treatment of patients with HER2 positive breast cancer. Identify the main adverse reactions presented by patients with HER2 positive breast cancer from an outpatient clinic specialized in chemotherapy in the city of Caruaru-PE, after the use of Trastuzumab. The data were obtained through the analysis of the medical records of the patients attended at the outpatient clinic from January to December Twenty-four patients were selected, of whom Identifying such adverse events makes it possible to better assist the oncological patient and to better adhesion to the treatment.
Because they are specific target drugs, few studies are concerned with evaluating these adverse events, which often makes clinical care difficult. Se seleccionaron 24 pacientes, de los cuales Antineoplastic chemotherapy consists of the use of cytotoxic drugs alone or in combination, which act on tumor cells.
In order to inhibit the proliferation of cancer cells, the cell cycle is one of the main foci in the action of antineoplastic agents.
I Diretriz Brasileira de Cardio-Oncologia da Sociedade Brasileira de Cardiologia
Each drug class will act at a particular stage of the cell cycle, not only acting on cancer cells, but also on normal cells of rapid proliferation. Therefore, these drugs produce undesirable side effects and are toxic to those taking such medications 1. Immunotherapy presents as the great proposal of treatment of some neoplasias with a focus on the decrease of adverse reactions. Tumor immunotherapy is based on the use of elements of the immune system to eliminate or neutralize tumor cells and factors that benefit tumor survival 2.
Monoclonal antibodies, as target therapy, have high specificity with few side effects, being the focus of many research on diseases that require more aggressive treatment. These agents are gaining space in the treatment of some types of cancer, as is the case of Trastuzumab in the treatment of breast cancer, Cetuximab in the treatment of colorectal cancer and Rituximab in the treatment of lymphomas 3. There are few studies that are concerned with the toxicity of monoclonal antibodies in the treatment of malignancies.
Therefore, this article aims to identify the main adverse reactions presented by pog in an outpatient clinic specialized in chemotherapy in the city of Caruaru-PE. This is a retrospective, quantitative and descriptive study based on the medical records of patients who used the monoclonal antibody Trastuzumab.
Data collection took place from February to Junein which the medical records of the patients of the Caruaru Oncology Center, who used the Trastuzumab antibody, were evaluated as isolated therapy or associated with other chemotherapeutic agents for trastuzumag treatment of breast cancer HER2 positive. A total of 59 patients attended at the outpatient clinic from January to Decemberwho used the monoclonal antibody Trastuzumab, associated or not with other antineoplastic agents, were excluded only patients who underwent hormone therapy, since hormone therapy alone, may be object of study in specific work, not being included trastuzumwb the objectives of this work.
The analysis of medical records sought data such as: Cardiotozicidad inclusion criteria used were female patients with HER2-positive breast cancer who used Trastuzumab in the treatment of their neoplasia, whether or not they were associated with other antineoplastic agents.
The established exclusion criteria were patients with other types of cancer that did not express the HER2 receptor, as well as smokers and patients who underwent antiestrogen therapy. After the retrospective analysis of the medical trastuzuumab, it was verified that of the 59 patients selected, only 24 met the established criteria.
It was verified that about 6 patients had hypertension and 2 had diabetes. Regarding the histological classification of cancer, 21 patients presented Ductal Invasive Carcinoma, figure 1 shows the main histological types presented by the patients.
Regarding the therapeutic approach, about 8 patients underwent a surgical procedure, of which 6 performed Radical Mastectomy and 2 underwent Quadrantectomy with axillary emptying. Regarding radiotherapy, 19 patients performed, of which 10 did before starting treatment with Trastuzumab and 9 discontinued the use of Trastuzumab for radiotherapy and returned to the administration of Trasuzumab after radiotherapy, in which the mean dosage was As for chemotherapy, the vast majority of patients had protocols with anthracyclines, as shown in figure 2in which the protocol Doxorubicin associated with Cyclophosphamide was one of the most used by the study patients.
After treatment with anthracycline protocols, trasyuzumab patients performed protocols with taxanes associated or not with Trastuzumab, of which 10 used Paclitaxel trastuzkmab 6 who used Docetaxel. During the administration of carsiotoxicidad doses of Trastuzumab, three patients discontinued the use of the monoclonal antibody due to a decrease in the ejection fraction after the tradtuzumab, 7th and 10th cycles, one presented pulmonary thromboembolism after the 6th cycle, another presented dysuria after the 7th cycle, traastuzumab patient had a seizure after the 12th cycle of Trastuzumab, in which an magnetic resonance imaging was performed on the skull showing the possibility of metastasis.
Another reported constipation after the second cycle, abdominal pain after cardiotxoicidad 7th cycle and nausea after the 9th cycle and another patient presented odynophagia after the 5th cycle of Trastuzumab. Currently, one of the major stakes in the treatment of cancer is immunotherapy, cardiotoxididad consists of stimulation of the immune system through the use of substances modifying the biological response, which may occur through the result of the antigen-antibody interaction or the mechanisms involved in the mediated immunity by cells 5.
Monoclonal antibodies are products based on modified immunoglobulins, which exert a specific effect on a specific cradiotoxicidad, which makes it one of the great bets in the treatment of certain tumors, as it decreases the adverse reactions caused by the antineoplastic chemotherapeutics.
The main antibodies used in the cadriotoxicidad are Cetuximab, Rituximab, Trastuzumab, Bevacizumab, among others 6. Trastuzumab is a humanized monoclonal antibody that acts on human epidermal growth factor receptor-2 HER2in which its target trqstuzumab the subdomain IV of the extracellular region of HER2, being indicated in the treatment of breast cancer with high expression of HER2 and in the treatment of adenocarcinoma of the gastroesophageal or metastatic gastric junction with high expression of HER2.
Its mechanism of action is associated with interference with signal transduction pathways, inhibition of extracellular domain cleavage, inhibition of DNA trawtuzumab, reduction of angiogenesis, induction of cell cycle arrest, activation of antibody-dependent cellular cytotoxicity 6. According to the study by Cintra et al 7the age range of patients with breast cancer with HER2 overexpression presents in two peaks 40 and 59 years and 70 years or older, which is consistent with the data collected in the study, trastuumab demonstrating the predominance of invasive ductal histological type with With respect to clinical staging, Santos et al 8 demonstrated a greater number of patients with stage III and II, corroborating the data collected in this study, presenting 13 patients in stage III and 9 patients with stage II as shown in figure 3.
These are new drugs in the clinic, for this reason, there is very little information on its side effects, although its mechanisms of action are very specific, these monoclonal antibodies are not free of side effects. Trastuzumab is often associated with significant cardiotoxicity, which is primarily responsible for premature termination of treatment, in which this effect may be related to arterial hypertension, age greater than 50 years, exposure to anthracyclines Doxorubicin, Epirubicin and Daunorubicin and baseline left ventricular ejection fraction 9.
According to the study by Ayres et al 10about Table 1 presents the main adverse events presented by the study patients, presenting results with some reactions different from those presented in the Ayres et al 10 study.
Cardiotoxicodad clinical studies have demonstrated that Trastuzumab can cause damage to the myocardium, with a reduction in the contractile force of the left ventricle, and it is possible to reverse this clinical situation after cardiotoxcidad suspension of the drug since there is no damage to the cardiomyocyte. One of the most used tests trastzumab the clinic for cardiotoxciidad cardiac evaluation of these patients is the echocardiogram because caridotoxicidad allows to evaluate not only the systolic function but also the diastolic function, the cardiac valves and the pericardium.
The examination is performed periodically following the cycles of chemotherapy with this aiming to detect early myocardial lesion, in which the initial attention is attributed to the systolic function, with the calculation of the ejection fraction, the shortening function, the cavity dimensions and ventricular volumes The analysis of the results of this retrospective study of the medical records of patients with HER2 positive breast cancer and the adverse reactions to the treatment with the monoclonal antibody Trastuzumab, concludes that the monitoring and notification of these adverse events, as well as the need for cardiological follow-up of these patients is of fundamental importance with a focus on the reduction of risks and the benefit of therapeutics.
Because they are specific target drugs, few studies are concerned with evaluating the possible adverse events caused by these agents, often correlating with other clinical situations of cancer patients. Based on data found in the research, a need to combine efforts among efforts among oncologists, cardiologists, nurses and clinical pharmacists was recognized, in order to identify these adverse events.
Antineoplastic drug residues inside homes of chemotherapy patients. Int J Hyg Environ Cardiotoxicodad.
Muerte súbita debida a cardiotoxicidad aguda inducida por antraciclinas
Eletronic Journal of Pharmacy. Immunotherapy of Cancer Review. Immunohistochemical profile and clinical-pathological variables in breast cancer.
tastuzumab Rev Assoc Med Bras. Rev Bras Oncol Clin. Trastuzumab induced cardiotoxicity in HER2 positive breast cancer patients attended in a tertiary hospital. Int J Clin Pharm. Cardiotoxicity of anticancer drugs: J Natl Cancer Inst.
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This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. Original Articles Adverse reactions for the use of the monoclonal trastuzumab antibody in the treatment of patients with HER2 positive breast cancer.
November 22, ; Accepted: