Urinary Neopterin in Patients with Metastatic Colon Cancer Treated with Patupilone

Abstract

Despite increased efficacy of regimens combining cytotoxic drugs and targeted agents, most patients with metastatic colorectal cancer will ultimately die of the disease. Only a limited number of drugs have reproducible activity in therapy of this tumor, and new active agents are urgently needed. Promising results in the therapy of metastatic colorectal cancer have been reported for patupilone, an epothilone analogue. Similarly to taxanes, the cytotoxic mechanism of epothilones involves the stabilization of microtubules. Increased serum or urinary concentrations of neopterin have been described in patients with tumors of different primary locations, including colorectal cancer. Neopterin concentrations were reported to increase during the administration of cytotoxic agents, including taxane-based chemotherapy. We have studied serum neopterin in patients with colorectal cancer before and during the therapy with patupilone. Urinary neopterin/creatinine concentrations were determined with highperformance liquid chromatography. Increased urinary neopterin concentrations were observed at baseline in the majority of the patients. In most patients, neopterin concentrations further increased during the therapy, and a significant increase of urinary neopterin was observed in patients with normal baseline neopterin concentrations. A trend of decreased survival was observed for patients with high initial neopterin concentration. In conclusion, urinary neopterin is increased in colorectal cancer patients presenting for second or higher line of treatment. An increase of urinary neopterin during patupilone therapy suggests an activation of immune response by this agent.

Keywords

• colon cancer
• neopterin
• patupilone