RESUMEN
BACKGROUND: The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer. PATIENTS AND METHODS: This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. RESULTS: In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%. CONCLUSIONS: Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Administración Oral , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Antineoplásicos/administración & dosificación , Bencenosulfonatos/administración & dosificación , Biomarcadores de Tumor/análisis , Canadá , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Resistencia a Antineoplásicos , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/irrigación sanguínea , Neoplasias Hormono-Dependientes/química , Neoplasias Hormono-Dependientes/inmunología , Neoplasias Hormono-Dependientes/patología , Neovascularización Patológica/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/irrigación sanguínea , Neoplasias de la Próstata/química , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridinas/administración & dosificación , Sorafenib , Resultado del TratamientoRESUMEN
The authors describe an A*68 allele present at the molecular level but not expressed at the cell surface. This non expression results from the deletion of one nucleotide in exon 1, which causes a shift of the reading frame leading to an early non-sense codon in the same exon.