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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Breast Neoplasms/drug therapy , Receptor, ErbB-2/analysis , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzenesulfonates/administration & dosage , Brazil , Breast Neoplasms/chemistry , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Double-Blind Method , Drug Administration Schedule , Europe , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Niacinamide/analogs & derivatives , Phenylurea Compounds , Proportional Hazards Models , Protein Kinase Inhibitors/administration & dosage , Pyridines/administration & dosage , Sorafenib , Time Factors , Treatment OutcomeABSTRACT
Sarcomas of the larynx are rare neoplasmas that consitute less than 1% of laryngeal malignancies, and their usual treatment is surgery including partial and total laryngectomy and endoscopic laser cordotomy with reported 20% recurrence. Due to previous positive experience from transversal laryngotomy in patients who underwent aritenoidectomy to treat bilateral cord paralysis after total thyroidectomy, the purpose of this work was to report on the surgical treatment of this rare case with such technique. Thus, a 47 year-old physician who complained of hoarseness for four months without dyspnea, stridor, or dysphagia and with no history of irradiation or chemotherapy was operated after both endoscopic and tomographic studies showed a 3 to 4 cm glotic tumor in its right side, with no ulceration. The pathology proved to be malignant fibrous histiocytoma. Five years after surgery the patient is alive with no evidence of disease.
Subject(s)
Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Sarcoma/diagnosis , Sarcoma/surgery , Humans , Male , Middle AgedABSTRACT
Los sarcomas de la laringe son neoplasias que constituyen menos del 1 por ciento de los tumores malignos, y su tratamiento habitual es quirúrgico que incluye la laringectomía parcial o total y la cordectomía endoscópica con láser, con recurrencias de hasta 20 por ciento. Debido a experiencia positiva en nuestro país con la laringotomía transversa en casos de aritenoidectomía para tratar parálisis bilateral de las cuerdas vocales como consecuencia de tiroidectomía total, el propósito de este reporte fue el de informar el resultado obtenido con esta técnica de laringotomía transversa a un caso raro de sarcoma glótico en un médico de 47 años que tenía cuatro meses de disfonía moderada sin disnea, disfagia ni estridor y sin historia de radioterapia o quimioterapia previas. La lesión fue evaluada por endoscopia y tomografía laríngea que mostraron un tumor del lado derecho de la glotis de 3 a 4 cm de tamaño no ulcerado. El informe patológico fue de un fibrohistiocitoma maligno. Cinco años después el paciente está bien y sin evidencia de enfermedad.