Urinary neopterin in patients with ovarian cancer

Abstract

Urinary neopterin, an indicator of systemic immune activation, is increased in most patients with epithelial ovarian carcinoma (EOC) and is an independent prognostic indicator. The data on prognostic significance of neopterin in EOC have been collected before the advent of paclitaxel that has changed the management and natural history of the disease. In the present study, we have evaluated the prognostic significance of urinary neopterin in 49 patients with primary and secondary ovarian neoplasms treated in the late 1990s and in 2000s. Urinary neopterin was measured by high-performance liquid chromatography. Compared to controls, urinary neopterin was significantly increased in patients with both primary ovarian cancer and ovarian metastases of other tumors (341 ± 343, and 328 ± 277 vs. 133 ± 40 μmol/mol creatinine; p <0.001). Serious toxicity of chemotherapy was observed in 8 out of 12 (67%) patients with urinary neopterin equal or above 338 μmol/mol creatinine (mean of all patients) compared to 2 of 19 (11%) of patients with urinary neopterin below 338 μmol/mol creatinine (Fisher exact test, p = 0.001). No significant changes were observed in urinary neopterin concentrations during the treatment with paclitaxel/platinum. A significant correlation was observed between urinary neopterin and percentage of xylose absorbed (rS = -0.58, p = 0.03), and positive correlations were observed between urinary neopterin and lactulose/mannitol (rS = 0.63, p = 0.02), lactulose/xylose (r S = 0.79, p = 0.0007) and sucrose/xylose (rS = 0.60, p = 0.02) ratios. Survival was significantly longer in patients with urinary neopterin below 338 μmol/mol creatinine in the whole group of 49 patients with ovarian cancer, in 36 patients with primary ovarian cancer as well as in 13 patients in ovarian metastases of other primary tumors. A significant difference in survival was also observed when 37 pretreated patients or 24 pretreated EOC patients were evaluated (p = 0.05). In conclusion, neopterin remains a significant prognostic indicator in patients with recurrent ovarian cancer in the era of newer chemotherapeutic agents. Increased urinary neopterin was associated with chemotherapy toxicity.