RESUMEN
BACKGROUND: We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4(+)CD25(HI)Foxp3(+) regulatory T cells and expanded melanoma-specific CD8(+) T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients. METHODS: In a single-center, phase II trial, DAB/IL2 (12 µg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[(18)F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging. RESULTS: After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; p value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year. CONCLUSIONS: These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma. TRIAL REGISTRATION: NCT00299689.
Asunto(s)
Antineoplásicos/uso terapéutico , Toxina Diftérica/uso terapéutico , Interleucina-2/uso terapéutico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Femenino , Humanos , Kentucky , Masculino , Melanoma/patología , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Proteínas Recombinantes de Fusión/uso terapéutico , Neoplasias Cutáneas/patología , Análisis de Supervivencia , Linfocitos T , Tomografía Computarizada por Rayos XRESUMEN
A case of early postoperative small bowel obstruction (SBO) after intraoperative use of hemostatic agents during laparoscopic staging for endometrial cancer is reported. A 46-year-old woman underwent a laparoscopic staging procedure for endometrial cancer during which hemostatic agents were used in the management of an iatrogenic injury to the inferior vena cava. The patient returned on postoperative day 6 with SBO and was taken to the operating department. She required a small bowel resection in the specific area where the hemostatic agents were used. Pathology showed extensive fibrotic changes caused by a foreign material that was suggestive of a thrombin-related product. Use of hemostatic agents should be considered as a cause in the differential diagnosis of patients with early postoperative SBO.