RESUMEN
PURPOSE: Inactivation of the von Hippel-Lindau gene in clear-cell renal cell carcinomas (RCC) leads to overexpression of hypoxia inducible factor, a transcription factor regulating vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) gene expression. Pazopanib, an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor, and c-KIT, was evaluated in patients with RCC. PATIENTS AND METHODS: This phase II study was designed as a randomized discontinuation study but was revised to an open-label study on the recommendation of the data monitoring committee (based on week 12 response rate [RR] of 38% in the first 60 patients). The primary end point was changed from progressive disease rate at 16 weeks postrandomization to RR. Pazopanib 800 mg was administered orally once daily. Pazopanib 800 mg was administered orally once daily. RESULTS: The study enrolled 225 patients with metastatic RCC; 155 patients (69%) were treatment naïve, and 70 patients (31%) had received one prior cytokine- or bevacizumab-containing regimen. Overall RR was 35%; median duration of response was 68 weeks. Median progression-free survival (PFS) was 52 weeks. Eastern Cooperative Oncology Group performance status of 0 and time from diagnosis to treatment of more than 1 year were correlated with prolonged PFS. Pazopanib was generally well tolerated. The most common adverse events were diarrhea, fatigue, and hair depigmentation. The most common laboratory abnormalities were elevated AST and ALT. CONCLUSION: Pazopanib demonstrated durable activity in patients with advanced RCC and was generally well tolerated in this population. These findings support the further development of pazopanib in advanced RCC.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/secundario , Femenino , Humanos , Indazoles , Neoplasias Renales/secundario , Masculino , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Resistencia a Antineoplásicos , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pirimidinas/uso terapéutico , Terapia Recuperativa , Sulfonamidas/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anciano , Femenino , Humanos , Indazoles , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/diagnóstico , Pronóstico , Seguridad , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
To compare the effect of ritonavir on plasma amprenavir pharmacokinetics, healthy adults received either fosamprenavir (700 mg twice a day [BID]) or amprenavir (600 mg BID) alone and in combination with ritonavir (100 mg BID). Ritonavir increased plasma amprenavir pharmacokinetic parameters to a similar extent when coadministered with either fosamprenavir or amprenavir.
Asunto(s)
Carbamatos/farmacología , Inhibidores de la Proteasa del VIH/farmacología , Organofosfatos/farmacocinética , Ritonavir/farmacología , Sulfonamidas/farmacología , Sulfonamidas/farmacocinética , Adulto , Área Bajo la Curva , Carbamatos/administración & dosificación , Estudios Cruzados , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Furanos , Humanos , Masculino , Persona de Mediana Edad , Organofosfatos/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificaciónRESUMEN
Single doses of MAALOX TC and ranitidine were administered separately with 1,400 mg of fosamprenavir (FPV). MAALOX TC decreased the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for plasma amprenavir (APV) by 18% and the maximum concentration of drug in serum (C(max)) by 35%; the plasma APV concentration at 12 h (C(12)) increased by 14%. Ranitidine at 300 mg decreased the AUC(0-24) for plasma APV by 30% and C(max) by 51%; C(12) was unchanged. FPV may be coadministered with antacids without concern and without separation in dosing; however, caution is recommended when FPV is coadministered with histamine(2)- receptor antagonists or proton pump inhibitors.
Asunto(s)
Hidróxido de Aluminio/farmacología , Antiácidos/farmacología , Antiulcerosos/farmacología , Inhibidores de la Proteasa del VIH/farmacocinética , Hidróxido de Magnesio/farmacología , Organofosfatos/farmacocinética , Ranitidina/farmacología , Sulfonamidas/farmacocinética , Hidróxido de Aluminio/administración & dosificación , Antiácidos/administración & dosificación , Antiulcerosos/administración & dosificación , Área Bajo la Curva , Carbamatos , Esquema de Medicación , Combinación de Medicamentos , Interacciones Farmacológicas , Furanos , Inhibidores de la Proteasa del VIH/administración & dosificación , Humanos , Hidróxido de Magnesio/administración & dosificación , Organofosfatos/administración & dosificación , Ranitidina/administración & dosificación , Sulfonamidas/administración & dosificación , Sulfonamidas/sangreRESUMEN
Hypersensitivity to abacavir affects about 4% of patients who receive the drug for HIV-1 infection. We did a retrospective, case-control study to identify multiple markers in the vicinity of HLA-B associated with hypersensitivity reactions. HLA-B57 was present in 39 (46%) of 84 patients versus four (4%) of 113 controls (p<0 small middle dot0001). However, because of low numbers of women and other ethnic groups enrolled, these findings relate largely to white men. The lower sensitivity of HLA-B57 for predicting hypersensitivity to abacavir identified in this study compared with a previous report highlights that predictive values for markers will vary across populations. Clinical monitoring and management of hypersensitivity reactions among patients receiving abacavir must remain unchanged.