Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review

Abstract

Advanced pancreatic cancer (PC) has a very poor prognosis due to its chemoresistant nature. Nowadays, only a few therapeutic options are available for PC, and the most effective ones are characterized by low response rates (RRs), short progression-free survival and overall survival, and severe toxicity. To improve clinical results, small series studies have evaluated loco-regional chemotherapy as a treatment option for PC, demonstrating its dose-dependent sensitivity towards the tumor. In fact, pancreatic arterial infusion (PAI) chemotherapy allows higher local concentrations of chemotherapeutic agents, sparing healthy tissues with a lower rate of adverse events compared to systemic chemotherapy. This therapeutic approach has already been evaluated in different types of tumors, especially in primary and metastatic liver cancers, with favourable results. With regard to advanced PC, a few clinical studies have investigated the safety and efficacy of PAI with promising results, especially in terms of RRs compared to systemic chemotherapy. However, clear evidence about its efficacy has not been established yet nor have the underlying mechanisms leading to its success. In this review, we aim to summarize the literature data on the clinical approaches to pancreatic arterial drug administration in terms of techniques, drug pharmacokinetics, and clinical outcomes for advanced PC.

Comparison of regional arterial chemotherapy and systemic intravenous chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis

“…Typically, preoperative arteriography of the celiac artery and superior mesenteric artery (SMA) is performed to observe the blood supply of the tumor and to select the target vessel. [13] Tanaka et al [32] attempted embolization of the pancreatic artery originating from the SMA to achieve a single supply of the celiac artery to the tumor. This study found that SMA embolization can not only increase the regional drug concentration of the tumor, but also have an effect on liver metastases.…”

Therapeutic Effect of Regional Chemotherapy in Diffuse Metastatic Cholangiocarcinoma

“…The regional chemotherapy (RegCTx) approach is an oncological approach with a very low toxicity profile and high tumour response due to high cytotoxic drug concentrations in an isolated perfusion bed [ 13 , 14 , 15 , 16 , 17 , 18 ]. In addition, the therapy can be focused on limited regions if necessary, using the same technique, e.g., hypoxic abdominal stop-flow perfusion (HAP), upper abdominal perfusion (UAP), isolated thoracic perfusion (ITP) and intra-arterial infusion.…”

“…The restricted perfusion bed that is treated during RegCTx allows potentiation of drug concentration levels at the tumour site compared to sCTx, despite using up to 20–50% lower overall cytotoxic drug amount. Furthermore, the possibility to perform a chemo-filtration ensures the lowest systemic toxicity effects [ 12 , 13 , 14 , 16 , 18 ]. RegCTx efficacy has been proven in many cancers but has not been reported in advanced metastatic CCC.…”

Regional Chemotherapy Is a Valuable Second-Line Approach in Metastatic Esophageal Cancer after Failure to First-Line Palliative Treatment

“…The regional chemotherapy (RegCTx) approach is an oncological approach with very low toxicity profile and high tumor response due to high cytotoxic drug concentrations in an isolated perfusion bed [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. In addition, the therapy can be focused on limited regions if necessary, using the same technique (e.g., upper abdominal perfusion (UAP), isolated thoracic perfusion (ITP), and intra-arterial infusion (AI)).…”

“…The restricted perfusion bed that is treated during RegCTx allows potentiation of drug concentration levels at the tumor site compared to sCTx despite using up to 20–50% of lower overall cytotoxic drug amount. Furthermore, the possibility to perform a chemo-filtration ensures lowest systemic toxicity effects [ 12 , 14 , 15 , 16 , 19 ]. RegCTx efficacy has been proven in many cancers including metastatic gastric cancer but has not been reported in advanced metastatic EC.…”