floxuridine
Sources réglementaires consultées
Indications approuvées
- Traitement palliatif d’un adénocarcinome gastro-intestinal métastatique au foie par perfusion intra-artérielle régionale continue chez des patients soigneusement sélectionnés.
Contre-indications
Absolues
- Mauvais état nutritionnel ; dépression médullaire ; infection potentiellement grave.
Mises en garde cliniques
- Arrêter en cas d’ischémie myocardique, premier signe de stomatite ou d’œsophagopharyngite, leucocytes <3 500 ou chute rapide, vomissements incontrôlables, diarrhée aqueuse, ulcère ou hémorragie GI, plaquettes <100 000 ou toute hémorragie. — DailyMed, set_id c8edabc1-67cd-421b-a147-7c1f19f05b8e
- Le cathétérisme artériel et la perfusion régionale exigent une hospitalisation initiale et une surveillance spécialisée des complications vasculaires, gastro-intestinales et hépatobiliaires. — DailyMed, set_id c8edabc1-67cd-421b-a147-7c1f19f05b8e
Grossesse et allaitement
Peut provoquer une atteinte fœtale ; éviter pendant la grossesse sauf nécessité critique. Ne pas allaiter pendant le traitement.
Bibliographie récente (PubMed)
The 3-year overall survival (OS) for advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver after systemic chemotherapy with gemcitabine-cisplatin (gem-cis) is only 3%. Hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine aims to control the liver disease and improve survival. The aim of this study was to assess the effectiveness of HAIP chemotherapy with floxuridine and concurrent systemic gem-cis in patients with unresectable liver-confined iCCA in the Netherlands. We performed a nonrandomized multicenter phase II trial. Treatment-naïve patients and patients previously treated with systemic therapy were eligible. Up to six cycles of HAIP floxuridine and eight cycles of concurrent systemic gem-cis were administered. The primary endpoint was 1-year OS compared with a historical cohort. From January 2020 to September 2022, 50 patients had a pump placed. Two patients (4%) did not start HAIP floxuridine; one patient died due to COVID-19, and one patient had a hepatic arterial dissection. The remaining 48 patients (96%) started HAIP chemotherapy, combined with systemic gem-cis in the 37 patients (74%) who had not received gem-cis previously. Twenty-two patients (44%) achieved a partial response and 42 patients (84%) disease control at 6 months. Five patients (10%) converted to resection, of whom one had a complete pathologic response. The median OS was 22.3 months (95% CI, 19.7 to 35.9 months). The 1-year OS of 80.0% (95% CI, 69.6% to 91.9%) was superior to the historical control of 47% (P < .001). The 3-year OS was 31.5% (95% CI, 20.4% to 48.6%). Combining HAIP chemotherapy with floxuridine and systemic gem-cis in patients with unresectable liver-confined iCCA had a 1- and 3-year OS superior to gem-cis alone in historical cohorts.
Nucleoside and nucleobase antimetabolites are an important class of chemotherapeutic agents for the treatment of cancer as well as other diseases. In order to avoid undesirable side effects, several prodrug strategies have been developed. In the present review, we describe a relatively unknown strategy that consists of using oligonucleotides modified with nucleoside antimetabolites as prodrugs. The active nucleotides are generated by enzymatic degradation once incorporated into cells. This strategy has attracted large interest and is widely utilized at present due to the continuous developments made in therapeutic oligonucleotides and the recent advances in nanomaterials and nanomedicine. A large research effort was made mainly in the improvement of the antiproliferative properties of nucleoside homopolymers, but recently, chemically modified aptamers, antisense oligonucleotides and/or siRNA carrying antiproliferative nucleotides have demonstrated a great potential due to the synergetic effect of both therapeutic entities. In addition, DNA nanostructures with interesting properties have been built to combine antimetabolites and enhancers of cellular uptake in the same scaffold. Finally, protein nanoparticles functionalized with receptor-binders and antiproliferative oligomers represent a new avenue for a more effective treatment in cancer therapy. It is expected that oligonucleotides carrying nucleoside antimetabolites will be considered as potential drugs in the near future for biomedical applications.
Hepatic artery infusion (HAI) delivers localized high-dose floxuridine directly to liver tumors through an implanted pump. While patients are undergoing active treatment, the pump is refilled with chemotherapy alternating with saline every 2 weeks using a specialized noncoring needle. Numerous clinical scenarios influence the dosing of floxuridine, which do not conform to the usual dose modification schema for systemic chemotherapy. This article aims to provide practical clinical management solutions to overcome the common challenges faced by oncologists in the real-world management of HAI pump therapy.
Intrahepatic cholangiocarcinoma is an aggressive malignancy with rising incidence and poor outcomes. This review examines recent advancements in locoregional therapies for unresectable intrahepatic cholangiocarcinoma, focusing on external beam radiotherapy, transarterial radioembolization (TARE), hepatic artery infusion pump (HAIP) chemotherapy, and liver transplantation. Stereotactic body radiation therapy and proton beam therapy have shown promise in achieving local control and improving survival. TARE, with personalized dosimetry, has demonstrated encouraging results in select patient populations. HAIP chemotherapy, primarily studied using floxuridine, has yielded impressive survival outcomes in phase II trials. Liver transplantation, once contraindicated, is now being reconsidered for carefully selected patients with localized disease. While these locoregional approaches show potential, randomized controlled trials comparing them to standard systemic therapy are lacking. Patient selection remains crucial, with factors such as liver function, tumor burden, and molecular profile influencing treatment decisions. Ongoing research aims to optimize treatment sequencing, explore combination strategies with systemic therapies, and refine phenotype identification and patient selection criteria. As the landscape of intrahepatic cholangiocarcinoma management evolves, a multidisciplinary approach is essential to tailor treatment strategies and improve outcomes for patients with this challenging disease.
Hepatic artery infusion (HAI) chemotherapy is a regional, intra-arterial treatment of hepatic malignancies, delivering high-dose floxuridine directly to the liver. The rationale for HAI is based on the dominant blood supply of liver tumors from the hepatic arteries and near complete first-pass hepatic extraction of certain chemotherapeutic agents, which limits systemic toxicity. Although HAI chemotherapy is most commonly used among patients with colorectal liver metastases, it is now being more frequently employed for other disease processes such as intrahepatic cholangiocarcinoma and hepatocellular carcinoma as well. In addition, HAI chemotherapy is most often used in the setting of unresectable hepatic malignancies.