Publication year: 2016
Theses and dissertations in Portugués presented to the Universidade Estadual de Campinas to obtain the academic title of Mestre. Leader: Zeferino, Luiz Carlos
Introdução:
O uso de trastuzumabe significou um ganho importante no prognóstico para a mulher com carcinoma de mama HER2-positivo, porém a cardiotoxicidade é o principal efeito adverso que pode determinar a interrupção do tratamento. O objetivo deste estudo foi analisar fatores associados ou decorrentes da cardiotoxicidade mediada pelo tratamento adjuvante com trastuzumabe em mulheres com carcinoma de mama. Metodologia:
O estudo incluiu 240 pacientes com carcinoma de mama HER2-positivo, estádios I, II e III, submetidas a terapia adjuvante com trastuzumabe. Todas mulheres incluídas tinham baseline ecocardiograma mostrando FEVE maior ou igual a 55%, sem sintomatologia ou manifestações clínicas de insuficiência cardíaca. A administração do trastuzumabe na terapia adjuvante foi de 8mg/kg no primeiro ciclo, seguido de 6mg/kg, totalizando 17 ciclos com intervalo de 21 dias. A avaliação clínica foi programada para ser realizada a cada 45 dias e o ecocardiograma a cada três meses. Resultados:
A frequência de cardiotoxicidade foi de 13.8% (33/240), sendo que em 28 pacientes devido a queda da FEVE abaixo de 55%, queda que foi revertida na maioria das pacientes com a suspensão ou interrupção do tratamento com trastuzumabe. O intervalo médio (DP) entre o início do tratamento com trastuzumabe e a queda da FEVE foi 7.33 (SD=3.70) meses. A hipertensão arterial esteve presente em 51.5% e 35.3% das pacientes que, respectivamente, apresentaram e não apresentaram cardiotoxicidade (p=0.07). Idade, peso, IMC, dislipidemia, diabetes mellitus, tabagismo, lateralidade da mama comprometida e estadiamento clínico não variaram significativamente com o diagnóstico de cardiotoxicidade. As pacientes que fizeram uso prévio de antraciclinas, apresentaram cardiotoxicidade em 15.4% enquanto as que fizeram uso de CMF apresentaram cardiotoxicidade em 5.3% (p=0.10). A cardiotoxicidade não apresentou associação com o tratamento com taxano e as doses acumuladas de antraciclinas foram semelhantes entre as pacientes. A cardiotoxicidade não apresentou associação com progressão da doença, recorrência local, recorrência regional e metástases. Observou-se que 28.1% das pacientes que apresentaram cardiotoxicidade evoluíram para óbito, o que ocorreu em 15.8% das pacientes que não tiveram cardiotoxicidade (p=0.09). O tratamento com trastuzumabe foi suspenso em 93.9% e 9.7% das pacientes que, respectivamente, apresentaram e não apresentaram cardiotoxicidade (p<0.0001). A média do total de ciclos de trastuzumabe aplicados nas pacientes que apresentaram cardiotoxicidade foram 10.9, enquanto que a média foi 16.0 para as pacientes que não apresentaram cardiotoxicidade, diferença que foi estatisticamente significante (p<0.0001). Conclusões:
As pacientes que apresentaram cardiotoxicidade realizaram menos ciclos de trastuzumabe, porém sem impacto negativo detectável no prognóstico do câncer de mama. Pacientes com hipertensão arterial seriam aquelas com maior probabilidade de desenvolver cardiotoxicidade. O desafio é balancear a suspensão ou interrupção do tratamento adjuvante com trastuzumabe, que melhora significativamente o prognóstico, com as manifestações clínicas da cardiotoxicidade(AU)
Introduction:
The use of trastuzumab has brought important gains in the prognosis of women with HER2-positive breast cancer, but cardiotoxicity is the main adverse effect that may determine discontinuing the treatment. This study aimed at analyzing factors associated with or derived from cardiotoxicity mediated by adjuvant trastuzumab therapy in HER2-positive breast cancer. Methodology:
The study included 240 patients with HER2-positive breast carcinoma, stages I, II and III, submitted to adjuvant trastuzumab therapy. All the women included had baseline echocardiograms showing a left ventricular ejection fraction (LVEF) greater than or equal to 55%, with no symptoms or clinical manifestations of cardiac insufficiency. Administration of trastuzumab in adjuvant therapy was given in dosages of 8mg/kg in the first cycle, followed by 6mg/kg, totaling 17 cycles with 21 day intervals. Clinical evaluations were scheduled for every 45 days and echocardiograms every three months. Results:
The cardiotoxicity frequency was 13.8% (33/240), of which 28 patients showed LVEF bellow of 55%, reduction that was reverted in most of the patients when suspending or interrupting the trastuzumab treatment. The average intervals (DP) between the beginning of trastuzumab treatment and the LVEF drop was 7.33 (SD=3.70) months. Hypertension was present in 51.5%, and 35.3% of the patients who, respectively, presented or did not present cardiotoxicity (p=0.07). Age, weight, body mass index, dyslipidemia, diabetes mellitus, tobacco use, laterality of compromised breast and clinical staging did not reveal statistically differences or association with cardiotoxicity diagnosis. We observed that 15.4% and 5.3% of patients who previously used, respectively, anthracycline and CMF showed cardiotoxicity (p=0.10). The cardiotoxicity showed no association with taxanes treatment and the accumulated dosages of anthracycline were similar among patients. Cardiotoxicity showed no association with the progression of the disease, local reoccurrences, regional reoccurrences or metastasis. We observed that 28.1% of the patients who presented cardiotoxicity died, while 15.8% of the patients who did not have cardiotoxicity also (p=0.09), but none of these death were directly caused by cardiotoxity. Trastuzumab therapy was suspended in 93.9% and 9.7% of the patients who, respectively, presented and did not present cardiotoxicity (p<0.0001). The average of total trastuzumab cycles applied in patients with cardiotoxicity was 10.9, while the average was 16.0 for patients who did not show cardiotoxicity, a statistically significant difference (p<0.0001). Conclusions:
Patients who presented cardiotoxicity received fewer trastuzumab cycles, but with no detectable negative impact on their breast cancer prognosis. Patients with hypertension seemed to be those most likely to develop cardiotoxicity. For the clinician the challenge is to balance the suspension or interruption of adjuvant therapy trastuzumab, which significantly improves the prognosis, with clinical symptoms of cardiotoxicity(AU)