Impact of itraconazole after first-line chemotherapy on the survival of patients with distant metastatic biliary tract cancer.

e15145

Background: The treatment of progressive biliary tract cancer (BTC) after first-line chemotherapy is under investigation. Itraconazole, a common antifungal agent, is a potent inhibitor of P-glycoprotein and the Hedgehog signaling pathway. We aimed to evaluate the efficacy and safety of itraconazole after first-line chemotherapy in patients with BTC. Methods: We retrospectively reviewed data from patients with histologically diagnosed metastatic BTC who had received ≥ 1 lines of chemotherapy and subsequent itraconazole chemotherapy. Results: Twenty-eight patients were enrolled. All these were referred to our institution from tertiary care hospitals. Twenty-three (82%) patients had progressive disease during prior chemotherapy, and 25 (89%) had an Eastern Cooperative Oncology Group performance status of 0. Twenty-six (93%) patients received docetaxel (35 mg/m²), gemcitabine (1,000 mg/m²), and carboplatin (area under the curve, 4 mg·min⁻¹·mL⁻¹) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2. Two patients received docetaxel plus itraconazole with irinotecan. The regimen was repeated every 2 weeks. Two complete responses and 14 partial responses were observed, with a response rate of 57%. Twenty-five (89%) patients switched cytotoxic regimens within 6 cycles. During 160 cycles, 19 (68%), 21 (75%), and 17 (61%) patients had grade 3/4 anemia, neutropenia, and thrombocytopenia, respectively. Nineteen (68%) patients received packed red blood cells, and two (7%) experienced febrile neutropenia. The median overall survival was 12.0 months. Conclusions: Combination chemotherapy with itraconazole after first-line chemotherapy demonstrated favorable efficacy with acceptable toxicities in patients with metastatic BTC.