RESUMO
BACKGROUND: Chemotherapy is standard neoadjuvant treatment of LA BC. Patients with HER2-positive BC require targeted therapy. Trastuzumab and pertuzumab, which target HER2, with chemotherapy are approved as neoadjuvant therapy, however, treatments with different mechanisms of action might provide a broader range of activity. In this study we evaluated the efficacy and safety of the irreversible ErbB family blocker afatinib, versus trastuzumab or lapatinib in the neoadjuvant treatment of HER2-positive, LA BC. PATIENTS AND METHODS: Treatment-naive, HER2-positive BC patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to daily afatinib (50 mg), lapatinib (1500 mg), or weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg/wk) for 6 weeks until surgery or follow-up neoadjuvant treatment. The primary end point was objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.0). RESULTS: Recruitment was stopped early because of slow patient enrollment; 29 patients were randomized to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Eleven patients had stable disease (best response); 1 lapatinib- and 1 trastuzumab-treated patient had progressive disease. All 10 afatinib-treated patients experienced drug-related adverse events (commonly diarrhea, dermatitis acneiform, and paronychia) versus 6 of 8 lapatinib- (diarrhea and rash) and 5 of 11 trastuzumab-treated patients (vomiting and arthralgia). CONCLUSION: Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive BC, with a safety profile consistent with epidermal growth factor receptor tyrosine kinase inhibitors.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinazolinas/uso terapêutico , Trastuzumab/uso terapêutico , Adulto , Afatinib , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Lapatinib , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Receptor ErbB-2/genéticaRESUMO
Este artigo faz uma revisäo dos mecanismos imunopatogênicos envolvidos na infecçäo por Giardia lamblia, aspectos da interaçäo parasita-hospedeiro e a aplicaçäo deste conhecimento no seu diagnóstico
