Outcomes of cancer patients treated with drotrecogin alfa (activated) for severe sepsis
Journal of Clinical Oncology. 2004;22((14_suppl)):6055
6055 Background: Drotrecogin alfa (activated) (Xigris; DAA), was approved for the treatment of severe sepsis in many countries based on a pivotal phase 3 trial of 1690 patients. DAA, has antithrombotic, profibrinolytic and anti-inflammatory properties and may improve microvascular thrombosis to reduce organ dysfunction in sepsis. We are reporting 1-month mortality outcomes among 303 patients with any prior or current history of malignancy enrolled in this pivotal trial (PROWESS). METHODS A post-hoc subgroup analysis was preformed on the 303 PROWESS cancer patients with acute sepsis-related organ dysfunction and who received standard therapy and either DAA at 24ug/kg/hr or placebo for 96 hrs. Patients were excluded for increased bleeding risk, including platelet count<30K/mm3, history of bone marrow transplant, poorly controlled neoplasm, or likely death from a non-sepsis cause within 28-days. Mortality and bleeding were evaluated at the 28-day PROWESS endpoint and mortality at 1-year. RESULTS Compared to the entire cohort cancer patients were older, had more chronic health points, and higher APACHE II scores. Cancer patients had a lower survival rate than the overall PROWESS group. Cancer patients experienced a significant treatment effect (28-day relative risk: 0.68) similar to the overall trial population (RR: 0.80). This benefit was similar at one year. Cancer and PROWESS patients experienced a similar rate of serious adverse bleeding events. CONCLUSIONS CONCLUSION DAA is efficacious and safe in patients with severe sepsis and early stage cancer or a history of malignancy. Despite increased baseline morbidity, DAA produced an increase in 28-day survival in cancer patients that was similar to the overall trial population. This treatment effect appeared to persist over the first year following the severe sepsis episode. [Figure: see text] [Table: see text].