Combination Chemotherapy with Itraconazole for Treating Metastatic Pancreatic Cancer in the Second-line or Additional Setting.

Abstract

We evaluated chemotherapy with itraconazole (a common anti-fungal agent that is a potent inhibitor of the Hedgehog pathway, P-glycoprotein, and angiogenesis) for treating progressive pancreatic cancer.We retrospectively reviewed the medical charts of patients with histologically-diagnosed pancreatic cancer who had received first- or second-line chemotherapy and subsequent chemotherapy with itraconazole.A total of 38 patients received docetaxel (35 mg/m(2)), gemcitabine (1,000 mg/m(2)), and carboplatin (area under the curve, 4 mg/min/ml) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2, repeated every 2 weeks. One complete response and 13 partial responses were observed, for a response rate of 37%. Eight (21%) patients experienced febrile neutropenia. The median overall survival was 11.4 months (95% confidence interval=8.5-21.2 months).Combination chemotherapy with itraconazole is promising for prolonging overall survival, with acceptable toxicities in the second-line setting of pancreatic cancer.