Pretreatment serum uPA and survival in patients with advanced pancreatic cancer

Abstract

4247 Background: Urokinase-type plasminogen activator (uPA) is a serine protease associated with tumor cell migration, angiogenesis, metastasis, and invasion. uPA has been reported to be secreted by tumors, adjacent stromal cells, and fibroblasts, and has been proposed as a prognostic factor in breast, liver, and colon cancers. Methods: This study determined serum uPA levels in a phase III clinical trial of 149 patients with advanced pancreatic cancer. A double-antibody sandwich ELISA (Oncogene Science Diagnostics, Cambridge, MA) was employed to determine the pretreatment serum uPA levels in 149 pancreatic cancer patients enrolled in a randomized, double-blind, placebo-controlled phase III trial. A healthy control group consisting of 47 males and 62 females was used to determine control serum levels of uPA. Results: The results showed that serum uPA levels were significantly higher in female (1.37 ng/mL) compared to male (1.15 ng/mL) healthy control individuals (p = 0.0002). Within the female control group, there was no significant difference in serum uPA levels between premenopausal (1.39 ng/mL, n = 47) and post-menopausal (1.31 ng/mL, n = 15) females (p = 0.39). Cutpoint analysis was performed separately using the mean + 2 SD for female (1.94 ng/mL) and male (1.74 ng/mL) controls. In the pancreatic cancer patients, serum uPA levels were elevated in 23 of 63 (36%) female patients, and 40 of 86 (46%) male patients. In addition, mean serum uPA levels were significantly higher in both female (1.85 ng/mL, p<0.00001) and male (1.96 ng/mL, p<0.00001) pancreatic cancer patients when compared to controls. Patients with elevated serum uPA trended toward a shortened survival (median 127 days) compared to patients with normal serum uPA levels (median 198 days)(p = 0.083). Conclusions: Serum uPA levels are significantly elevated in a proportion of advanced pancreatic cancer patients, and these patients trend toward shortened survival. Serum uPA levels may have potential for selection of patients to be treated with novel uPA small-molecule inhibitors. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp.; Oncogene Science/Bayer HealthCare Oncogene Science/Bayer HealthCare Novartis Pharmaceuticals Corp.