A phase II study has demonstrated that hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine offers significant improvements in overall survival (OS) for patients with advanced intrahepatic cholangiocarcinoma (iCCA). Bas Groot Koerkamp, MD, PhD, of the Erasmus MC Cancer Institute in Rotterdam, the Netherlands, reported that patients treated with HAIP chemotherapy combined with systemic chemotherapy achieved an impressive 1-year OS rate of 80%, compared to only 47% in the historical cohort treated with systemic chemotherapy alone. The study’s 3-year OS rates were equally dramatic, with a rate of 33% observed in the HAIP chemotherapy group, compared to a dismal 3% in the systemic chemotherapy group.
Koerkamp acknowledged the growing enthusiasm surrounding immunotherapy and targeted treatments in the field of intrahepatic cholangiocarcinoma. However, he emphasized that none of these treatments have demonstrated a 3-year overall survival rate of one in three patients for advanced disease. In contrast, HAIP chemotherapy has shown efficacy in patients regardless of their genomic alterations. While systemic chemotherapy is currently the standard of care for advanced iCCA, the median OS rate is only 16.7 months, with 1-, 2-, and 3-year rates of 63%, 25%, and 3%, respectively. This serves as the benchmark for new treatment options, including HAIP chemotherapy.
Prior phase II studies evaluating HAIP chemotherapy consistently reported an approximately 50% response rate and 3-year OS rates ranging from 29% to 43%. Koerkamp’s study aimed to replicate these promising results. HAIP involves the surgical implantation of a pump connected to the hepatic artery via a small catheter. This configuration enables the delivery of high-dose chemotherapy directly to the liver, minimizing the toxicities associated with systemic treatment. The rationale behind this approach lies in the fact that liver tumors primarily receive their blood supply from the hepatic artery. Additionally, the drug floxuridine exhibits a high first-pass effect, leading to a 200-fold higher exposure within cancer cells.
The study enrolled 50 patients with unresectable iCCA confined to the liver. The patients, with a median age of 65, received six cycles of HAIP chemotherapy in combination with eight cycles of systemic chemotherapy. Notably, 48 patients successfully initiated HAIP, and 42 received at least four cycles of the treatment. Among the participants, 22% had previously undergone systemic chemotherapy, and complications were observed in 22% of the patients, resolved with reintervention. The study reported a partial response in 46% of patients, surpassing the response rate observed with gemcitabine/cisplatin alone (21%) and aligning with the rates reported in published phase II trials investigating HAIP chemotherapy.
During the question and answer session following the presentation, Benjamin Schlechter, MD, of the Dana-Farber Cancer Institute in Boston, inquired about the comparison between HAIP and selective internal radiation therapy (SIRT) using yttrium-90 (Y-90). Schlechter suggested that liver-directed therapy offers clear benefits over systemic therapy, noting that there have been no direct comparisons between Y-90 and HAIP. Despite this, he opined that the results from HAIP chemotherapy are more robust, primarily due to its ability to treat the entire liver. Koerkamp further clarified that SIRT with Y-90 is reserved for cases where the lesion is encroaching on the hilum and HAIP is not a feasible option.
The study’s findings highlight the potential of HAIP chemotherapy as a promising treatment option for patients with advanced intrahepatic cholangiocarcinoma. The significant improvements in overall survival observed compared to systemic chemotherapy alone make it an attractive alternative. While further research is needed, HAIP chemotherapy offers a vital option for patients with iCCA, particularly those who are not candidates for surgical resection. As the field of oncology continues to evolve, advancements like HAIP chemotherapy open doors to better outcomes for cancer patients.
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