What can be expected from intra-arterial chemotherapy?

Intra-arterial hepatic chemotherapy (IAHC) was developed at a time when intravenous chemotherapy had only modest efficacy. Initially, the practical method involved surgical implantation of a catheter connected to a perfusion pump using FUDR. This method continues to be used in the United States; it is relatively expensive, requiring pump implantation (not covered by health insurance) and the use of FUDR, which has shown some efficacy but also carries a risk of toxicity, particularly biliary toxicity. In parallel, the implantation of catheters connected via a subcutaneous access has been developed. This subcutaneous access allows connection to an external infusion pump, thus enabling the use of various chemotherapy drugs: 5-fluorouracil, irinotecan, oxaliplatin, or mitomycin C. The first catheters connected to this subcutaneous access were also placed surgically, and later a catheter model was made available to interventional radiologists. This catheter, of Japanese origin, connected to a subcutaneous access in the iliac fossa, allowed interventional radiologists to implant it under excellent conditions for patients and with very high reliability. This catheter is no longer available, and hepatic IAHC is now administered either with a lower-quality catheter implanted by interventional radiologists, which is not always very reliable, or through repeated catheter insertion sessions and short-duration intra-arterial infusions.
In terms of outcomes, in first-line metastatic treatment, IAHC was slightly more effective than intravenous chemotherapies of the 1990s in terms of objective response, without any advantage in terms of overall survival. The use of oxaliplatin, which achieved a median progression-free survival of over 20 months in the first study, is currently being evaluated in a randomized trial. Beyond first-line treatment, IAHC, particularly with oxaliplatin, provides promising responses, especially in patients requiring intensification of their treatment or those with disease refractory to conventional chemotherapy in the nth line, either as a therapeutic strategy enabling secondary resection or in terms of disease control in completely refractory patients.
One potential use for IAHC is, of course, after resection of liver metastases. Here again, a meta-analysis of randomized trials using FUDR did not show a major effect, although a positive trend exists. More recent real-world studies, whether with the implantable pump or with oxaliplatin and surgically or radiologically implanted catheters, have shown a benefit in favor of intra-arterial chemotherapy. Most notably, a recently published randomized trial (the PACHA trial) systematically randomized postoperative intra-arterial administration of oxaliplatin versus intravenous FOLFOX. This trial proved positive in terms of liver recurrence-free survival, with a borderline significant effect in terms of progression-free survival and overall survival. A larger randomized confirmatory trial (PACHA2) was funded by the ARCAD Foundation and should be able to definitively answer the question of the benefit of IAHC with oxaliplatin after complete resection of liver metastases.
In conclusion, IAHC is a chemotherapy administration technique which, in a number of situations, complements the medical-surgical strategy of treatment of liver metastases of colorectal either to control the disease for longer or to allow an additional cure rate in resected patients.