M Martín1, P Sánchez-Rovira2, M Muñoz3, J M Baena-Cañada4, J R Mel5, M Margeli6, M Ramos7, E Martínez8, J A García-Saenz9, A Casado9, A M Jaén2, X González-Farré3, M J Escudero10, C Rodriguez-Martin10, E Carrasco10. 1. Medical Oncology Department, Hospital Clínico San Carlos, Madrid. Electronic address: mmartin@geicam.org. 2. Medical Oncology Departmanet, Complejo Hospitalario de Jaén, Jaén. 3. Medical Oncology Department, Hospital Clinic i Provincial, Barcelona. 4. Medical Oncology Department, Hospital Puerta del Mar, Cádiz. 5. Medical Oncology Department, Hospital Xeral Calde, Lugo. 6. Medical Oncology Department, Hospital Germans Trias y Pujol, Badalona. 7. Medical Oncology Department, Centro Oncologico de Galicia, A Coruña. 8. Medical Oncology Department, Hospital Provincial de Castellón, Castellón. 9. Medical Oncology Department, Hospital Clínico San Carlos, Madrid. 10. GEICAM, Madrid, Spain.
Abstract
BACKGROUND: In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC). METHODS: PLD 50 mg/m(2) and cyclophosphamide 600 mg/m(2) were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety. RESULTS: Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9-15.1 months), and the median OS was 34.2 months (95% CI 27.2-41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand-foot syndrome in 29.2% of patients, and grade 3-4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction. CONCLUSION: The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.
BACKGROUND: In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in humanepidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC). METHODS: PLD 50 mg/m(2) and cyclophosphamide 600 mg/m(2) were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety. RESULTS: Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9-15.1 months), and the median OS was 34.2 months (95% CI 27.2-41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand-foot syndrome in 29.2% of patients, and grade 3-4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction. CONCLUSION: The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.
Authors: Sandra M Swain; Sung-Bae Kim; Javier Cortés; Jungsil Ro; Vladimir Semiglazov; Mario Campone; Eva Ciruelos; Jean-Marc Ferrero; Andreas Schneeweiss; Adam Knott; Emma Clark; Graham Ross; Mark C Benyunes; José Baselga Journal: Lancet Oncol Date: 2013-04-18 Impact factor: 41.316
Authors: Juan Lao; Julia Madani; Teresa Puértolas; María Alvarez; Alba Hernández; Roberto Pazo-Cid; Angel Artal; Antonio Antón Torres Journal: J Drug Deliv Date: 2013-03-26