Intra-arterial approach to locally advanced pancreatic cancer

Ripal Gandhi

The use of catheter-based localised delivery of drugs for treatment of cancer patients has proven to be effective and provides the benefit of reduced systemic toxicity. A critical prerequisite for these modalities is the angiographic identification and engagement of feeder vessels of appropriate size into the tumours in order to deliver the designated therapy. Therefore, hypovascular tumours are not optimally treated with these catheter-based techniques. For instance, pancreatic tumours, unlike their liver counterpart, are generally hypovascular, and are without any obvious arterial feeder vessels. Novel approaches to overcome this obstacle for drug delivery in these tumours has the potential to significantly improve outcome and potentially survival in these patients.

One such approach currently being investigated is trans-arterial micro-perfusion (TAMP). TAMP first isolates an artery of interest using a double balloon catheter to occlude the proximal and distal part of the vessel, followed by exclusion of major side branches. Upon infusion of drugs between the balloons in this isolated section, the increased intravascular pressure permits active diffusion of infusate directly across the vessel wall into the surrounding tissue.

Early studies of TAMP using gemcitabine chemotherapy in patients with locally advanced pancreatic cancer (LAPC), has shown the approach to be safe with no obvious local toxicity.

Currently, a phase III clinical trial, TIGeR-PaC, is comparing the efficacy of this approach using intra-arterial gemcitabine (IAG) versus standard of care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC. The trial is designed with an induction phase for all patients of upfront systemic chemotherapy and radiation prior to randomisation to IAG or continuation of GN. LAPC patients receive three cycles of GN and one cycle of radiation (stereotactic body radiation therapy; 33Gy in five fractions). Following induction, patients with non-progressive disease are randomised to receive IAG (eight treatments biweekly for 16 weeks) or continuation of GN for four cycles over 16 weeks. After the 16 weeks of randomised therapy, patients with non-progressive disease receive continuation systemic therapy of GN or low-dose oral capecitabine, per investigator’s preference until disease progression and are followed for survival only.

Recently, the first interim analysis of the trial was presented at the World Congress on Gastrointestinal Cancer (28 June–1 July, Barcelona, Spain). At the time, 45 patients had been randomised in the trial; the survival, progression-free survival (PFS) and the adverse events data (AE) comparing the two arms were presented. Of the 45 patients randomised, 23 were randomised to IAG and 22 to GN. There were equal number of primary events (13) in each arm. Patients enrolled in the study were randomised after the induction phase that lasted, on average, 5.5 months.

After randomisation, the median survival in the control arm is 10 months, vs. 16 months in the IAG arm. The p values based on Wilcoxson non-proportional hazard ratio (HR) is 0.08 between the two arms. The PFS in control arm was seven months vs. 15 months in IAG (HR 0.55; confidence interval [CI]: 0.21–1.47). There was a threefold increase in AE in the control arm versus IAG (245 vs. 85); most of difference in AE were haematological (neutropaenia and thrombocytopaenia), followed by transaminitis. Lastly, in term of tolerability of completing all four cycles of active treatment without treatment modification, 61% of patients in IAG completed all intended treatment vs. 18 % of the patients in GN. The first interim look at the trial results is very encouraging in favour of IAG. Currently, the trial continues to enrol in 17 centres in the USA, with a second interim look at the data expected at end of 2024.

Ripal Gandhi is a vascular and interventional radiologist at Miami Cardiac and Vascular Institute and Miami Cancer Institute (Miami, USA).


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