In a recent phase II study, researchers found that hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine showed promising results in improving overall survival (OS) among patients with advanced intrahepatic cholangiocarcinoma (iCCA). This treatment approach, when combined with systemic chemotherapy, demonstrated a substantial increase in the 1-year OS rate compared to the standard of care. The findings of this study provide new insights into the potential benefits of HAIP chemotherapy in patients with advanced iCCA.
The standard treatment for advanced iCCA is systemic chemotherapy, which has been associated with a median OS of 16.7 months and 3-year OS rates of 63%, 25%, and 3%. Although immunotherapy and targeted treatments have shown promise in treating iCCA, none of them have achieved a 3-year overall survival rate of one in three patients for advanced disease. In contrast, HAIP chemotherapy has shown consistent response rates of around 50% and 3-year OS rates ranging from 29% to 43% in previous phase II studies.
HAIP chemotherapy involves the implantation of a pump connected to the hepatic artery, allowing for the direct delivery of high-dose chemotherapy to the liver. This targeted approach minimizes the toxicities associated with systemic treatment and takes advantage of the fact that liver tumors derive most of their blood supply from the hepatic artery. In addition, the drug floxuridine has a high first-pass effect, providing a 200-fold higher exposure in cancer cells.
The phase II study included 50 patients with unresectable iCCA confined to the liver, treated between January 2020 and September 2022 in three Dutch academic centers. These patients received 6 cycles of HAIP chemotherapy in addition to 8 cycles of systemic chemotherapy. The median age of the participants was 65, with two-thirds having multifocal disease and 22% receiving prior systemic chemotherapy. The study found that patients treated with HAIP chemotherapy achieved a 1-year OS rate of 80% compared to 47% in the historical cohort treated with systemic chemotherapy. The 3-year OS rates were 33% and 3%, respectively. Additionally, 46% of patients showed a partial response, which was superior to the response rate observed with gemcitabine/cisplatin alone.
During a post-presentation discussion, the question arose about how HAIP chemotherapy compares to selective internal radiation therapy (SIRT) with yttrium-90 (Y-90). While no head-to-head comparisons have been conducted between these two therapies, HAIP chemotherapy was deemed to have more robust data. One advantage of HAIP over SIRT is that it treats the entire liver, making it a suitable option when large lesions are encroaching on the hilum and the pump cannot be used. Nevertheless, both therapies have shown efficacy in the treatment of iCCA.
The results of this phase II study highlight the potential benefits of HAIP chemotherapy in patients with advanced iCCA. The combination of HAIP and systemic chemotherapy showed significant improvements in 1-year and 3-year overall survival rates compared to standard systemic chemotherapy alone. With its targeted approach and high response rates, HAIP chemotherapy represents a promising treatment option for patients with unresectable iCCA confined to the liver. Further research and clinical trials are warranted to validate these findings and explore the optimal integration of HAIP chemotherapy into the treatment landscape of iCCA.
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