RESUMO
BACKGROUND: Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer. Strategies to improve efficacy include the use of anthracyclines, taxanes, and intensified dose with bone marrow support. PATIENTS AND METHODS: Patients received neoadjuvant epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) followed by paclitaxel 175 mg/m(2) (ECâT), each 3-weekly for four cycles (n = 370), or epirubicin 150 mg/m(2) followed by paclitaxel 225 mg/m(2) with pegfilgrastim followed by CMF (cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), fluorouracil 600 mg/m(2)) on days 1 and 8 (E(dd)âT(dd)âCMF), each 2-weekly and for three cycles (n = 363). Patients were randomly allocated to either simultaneous darbepoetin alfa (DA) (n = 356) or none (n = 377). RESULTS: Pathological complete response (pCR) rate (breast) was higher with E(dd)âT(dd)âCMF, 18.7% versus 13.2% with ECâT; P = 0.043, ypT0/Tis; ypN0 was reported in 20.9% versus 14.3% respectively; P = 0.019. Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate. Mean hemoglobin values maintained higher with DA (13.6 versus 12.6 g/dl). E(dd)âT(dd)âCMF regimen showed more grade 3-4 mucositis, sensory neuropathy, and neurological complaints. Thromboembolic events were more frequent on DA (3% versus 6%; P = 0.055). CONCLUSION: Dose-dense and -intensified neoadjuvant chemotherapy with E(dd)âT(dd)âCMF was potentially superior to ECâT in terms of pCR. Primary use of DA did not affect pCR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Darbepoetina alfa , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Eritropoetina/administração & dosagem , Eritropoetina/análogos & derivados , Feminino , Filgrastim , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hemoglobinas/metabolismo , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Cooperação do Paciente , Polietilenoglicóis , Cuidados Pré-Operatórios , Proteínas Recombinantes/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: The objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of standard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or without darbepoetin on survival in primary breast cancer. PATIENTS AND METHODS: A total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks followed by four cycles of paclitaxel 175 mg/m(2) every 3 weeks (ECâT), or three cycles of epirubicin 150 mg/m(2) every 2 weeks followed by three cycles of paclitaxel 225 mg/m(2) every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (E(dd)âT(dd)âCMF). The patients were randomly assigned to receive darbepoetin or none. The primary objective was to demonstrate a superior disease-free survival (DFS) of E(dd)âT(dd)âCMF compared with ECâT. RESULTS: Estimated 3-year DFS was 75.8% with ECâT versus 78.8% with E(dd)âT(dd)âCMF [hazard ratio (HR) 1.14; P = 0.37] and overall survival (OS) 88.4% versus 91.5% (HR 1.26; P = 0.237). Three-year DFS was 74.3% with darbepoetin versus 80.0% without (HR 1.31; P = 0.061) and OS 88.0% versus 91.8% (HR 1.33; P = 0.139). Patients with a pathologically documented complete response [pathological complete response (pCR)] had a significantly better DFS compared with those without achieving a pCR (estimated 3-year DFS: 89.2% versus 74.9%; HR 2.27; P = 0.001). CONCLUSION: Neoadjuvant dose-intensified chemotherapy compared with standard chemotherapy did not improve DFS, whereas the addition of darbepoetin might have detrimental effects on DFS.