RESUMEN
We conducted a pilot phase II trial of trastuzumab administered concurrently with docetaxel in women with HER2-overexpressing advanced breast cancer. Twenty-five women with HER2-positive (3+ by immunohistochemistry = 16, 2+ = 9) metastatic breast cancer received docetaxel (75 mg/m every 3 weeks for 6 cycles) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). Twenty-three patients (92%) had visceral metastatic involvement. Twenty-three patients had received prior chemotherapy as part of adjuvant (18), metastatic (2), and both (3) treatment. The number of cycles administered was 121 (median 6, range 1-6). Symptomatic cardiotoxicity (GIII) occurred in one patient. The most common grade GIII/IV toxicity was neutropenia (80% of the cycles), although febrile neutropenia did not occur. No other GIII/IV toxicities were observed. Response rate was 70% (1 complete response and 15 partial responses) in 23 evaluable patients. The combination of docetaxel and trastuzumab is well tolerated and has clinically meaningful antitumor activity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Genes erbB-2 , Paclitaxel/análogos & derivados , Taxoides , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/patología , Docetaxel , Femenino , Expresión Génica , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Proyectos Piloto , TrastuzumabAsunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/patología , Toma de Decisiones , Progresión de la Enfermedad , Esquema de Medicación , Medicina Basada en la Evidencia , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2 , TrastuzumabRESUMEN
BACKGROUND: To test safety and activity of 3-weekly doses of docetaxel and a weekly dose of trastuzumab in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty-two women, median age 53 years (range 36-73 years), with HER2-overexpressing advanced breast cancer were enrolled in a study of docetaxel, 75 mg/m(2) q3w for 6 cycles, and trastuzumab, 4 mg/kg loading dose, 2 mg/kg weekly thereafter. Thirty-four patients (81%) had visceral metastatic involvement. Thirty-five patients had received prior chemotherapy as part of their treatment: adjuvant/neoadjuvant (26), metastatic (2) and both (7). Thirty-one patients had been previously exposed to an anthracycline and 11 to paclitaxel. Four patients had previously received high-dose chemotherapy followed by autologous stem cell transplant. RESULTS: 226 cycles (median 6, range 1-6) were administered. The median delivered dose intensity for docetaxel was 24 mg/m(2)/week (range 16-25 mg/m(2)/week). The intent to treat overall response rate was 67% (95% confidence interval, 52-79%). Median progression-free survival, time to treatment failure, and duration of response were 9, 8 and 12 months, respectively. Symptomatic cardiotoxicity (grade 3) occurred in 1 patient. The most common grade 3/4 toxicity was neutropenia (76% of the patients), although febrile neutropenia did not occur. CONCLUSIONS: Three-weekly doses of docetaxel and a weekly dose of trastuzumab is an active and safe combination in patients with HER2-overexpressing advanced breast cancer.