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Title: Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer
Authors: BASELGA, JoseSEGALLA, Jose Getulio MartinsROCHE, HenriGIGLIO, Auro delPINCZOWSKI, HelioCIRUELOS, Eva M.CABRAL FILHO, SebastiaoGOMEZ, PatriciaEYLL, Brigitte VanBERMEJO, BegonaLLOMBART, AntonioGARICOCHEA, BernardoDURAN, Miguel Angel ClimentHOFF, Paulo Marcelo GehmESPIE, MarcMORAES, Andre Augusto Junior Gemeinder deRIBEIRO, Ronaldo AlbuquerqueMATHIAS, ClarissaGIL, Miguel GilOJEDA, BelenMORALES, JosefaRO, Sunhee KwonLI, ShellCOSTA, Frederico
Citation: JOURNAL OF CLINICAL ONCOLOGY, v.30, n.13, p.1484-1491, 2012
Abstract: Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.
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Artigos e Materiais de Revistas Científicas - FM/MDR
Departamento de Radiologia - FM/MDR

Artigos e Materiais de Revistas Científicas - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Artigos e Materiais de Revistas Científicas - HC/InRad
Instituto de Radiologia - HC/InRad

Artigos e Materiais de Revistas Científicas - LIM/24
LIM/24 - Laboratório de Oncologia Experimental

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