INTRA-ARTERIAL CHEMOTHERAPY IN ADVANCED PANCREATIC CANCER: A LITERATURE REVIEW
DOI:
https://doi.org/10.15407/exp-oncology.2025.04.421Keywords:
intra-arterial chemotherapy, regional chemotherapy, hepatic arterial infusion, pancreatic arterial infusion, advanced pancreatic cancerAbstract
Pancreatic cancer is an extremely aggressive malignancy with a 5-year survival rate among all stages of about 7%. Treatment options for unresectable forms are limited to fluoropyrimidine- and gemcitabine-containing regimens, and starting from the 3rd line, international guidelines do not provide clear recommendations because of the poor clinical condition of patients and the low efficacy of the consecutive lines. The arterial infusion is a promising method of treatment for locally advanced or liver-only metastatic disease, providing a higher local concentration with the same or lower systemic toxicity. The most often used intra-arterial regimens are those based on 5-fluorouracil and gemcitabine. This method was found to be superior in overall survival, response rate, and control of local symptoms compared to control groups treated with systemic chemotherapy. The approach has a good safety profile and is well tolerated. The method is promising for patients with an adequate performance status, who have run out of other potential regimens, in cases without distant metastases or liver-only metastatic disease, and for upcoming clinical trials or studies.
References
Pancreatic Cancer UK. Pancreatic cancer statistics [Internet]. Pancreatic Cancer UK. 2023. Available from: https:// www.pancreaticcancer.org.uk/what-we-do/media-centre/pancreatic-cancer-statistics/
Johns Hopkins Medicine. Pancreatic Cancer Prognosis [Internet]. www.hopkinsmedicine.org. Available from: https:// www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer/pancreatic-cancer-prognosis
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. https://doi.org/10.3322/ caac.21590
Chin V, Nagrial A, Sjoquist K, et al. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Rev. 2018;3(3):CD011044. https://doi.org/10.1002/14651858.CD011044.pub2
Pancreas [Internet]. Available from: https://gco.iarc.fr/today/data/factsheets/cancers/13-Pancreas-fact-sheet.pdf
Fedorenko ZP, Goulak LO, Gorokh YeL, et al. Cancer in Ukraine 2021-2022: incidence, mortality, prevalence and other relevant statistics. Bull Nat Cancer Reg Ukraine 2023: 24. Available at http://ncru.inf.ua/publications/ BULL_24/index_e.htm
NCCN Guidelines Version 1.2025 Pancreatic Adenocarcinoma. Nccn.org. 2024. Available from: https://www.nccn. org/professionals/physician_gls/pdf/pancreatic.pdf
Conroy T, Pfeiffer P, Vilgrain V, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(11). https://doi.org/10.1016/j.annonc.2023.08.009
Wei Y, Xiao Y, Wang Z, et al. Chinese expert consensus of image-guided irreversible electroporation for pancreatic cancer. J Cancer Res Ther. 2021;17(3):613-618. https://doi.org/10.4103/jcrt.JCRT_1663_20
Stewart DJ, Benjamin RS, Zimmerman S, et al. Clinical pharmacology of intra-arterial cis-diammine- dichloroplatinum(II). Cancer Res. 1983;43(2):917-920.
Liu F, Tang Y, Sun J, et al. Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2012;7(7):e40847. https://doi. org/10.1371/journal.pone.0040847
Kemeny NE, Niedzwiecki D, Hollis DR, et al. Hepatic arterial infusion versus systemic therapy for hepatic metas- tases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol. 2006;24(9):1395-1403. https://doi.org/10.1200/JCO.2005.03.8166
Wang N, Xu J, Wang G, Cao P, Ye X. Pancreatic intra-arterial infusion chemotherapy for the treatment of pa- tients with advanced pancreatic carcinoma: A pilot study. J Cancer Res Therap. 2022;18(7):1945-1951. https://doi. org/10.4103/jcrt.jcrt_819_22
Qiu B, Zhang X, Tsauo J, et al. Transcatheter arterial infusion for pancreatic cancer: a 10-year National Cancer Center experience in 115 patients and literature review. Abdom Radiol (NY). 2019;44(8):2801-2808. https://doi. org/10.1007/s00261-019-02022-2
Disibio G, French SW. Metastatic patterns of cancers: results from a large autopsy study. Arch Pathol Lab Med. 2008;132(6):931-939. https://doi.org/10.5858/2008-132-931-MPOCRF
Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954;30(5):969-977.
Ensminger WD, Gyves JW. Clinical pharmacology of hepatic arterial chemotherapy. Semin Oncol. 1983;10(2): 176-182.
Li S, Xu J, Zhang H, et al. The role of hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcino- ma: a systematic review and meta-analysis. Chemotherapy. 2021;66(4):124-133. https://doi.org/10.1159/000518257
NCCN Guidelines Version 6.2024 Colon Cancer. Nccn.org. 2024. Available from: https://www.nccn.org/profes- sionals/physician_gls/pdf/colon.pdf
Cervantes A, Adam R, Roselló S, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagno- sis, treatment and follow-up. Ann Oncol. 2023;34(1):10-32. https://doi.org/10.1016/j.annonc.2022.10.003
Boige V, Malka D, Elias D, et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol. 2008;15(1):219-226. https://doi.org/10.1245/s10434-007-9581-7
Aigner KR, Gailhofer S, Selak E, Aigner K. Intra-arterial infusion chemotherapy versus isolated upper abdominal perfusion for advanced pancreatic cancer: a retrospective cohort study on 454 patients. J Cancer Res Clin Oncol. 2019;145(11):2855-2862. https://doi.org/10.1007/s00432-019-03019-6
Cantore M, Fiorentini G, Bassi C, Molani L, Aitini E, Morandi C, et al. Intra-arterial Chemotherapy for Stage-lll/IV Pancreatic Cancer. Digestive Surgery. 1997;14(2):113-118. https://doi.org/10.1159/000172524
Homma H, Doi T, Mezawa S, et al. A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization. Cancer. 2000;89(2):303-313.
Han GH, Yin ZX, Meng XJ, et al. Prospective randomized clinical trial of two drug delivery pathway in the treat- ment of inoperable advanced pancreatic carcinoma. Chin J Dig Dis. 2006;7(1):45-48. https://doi.org/10.1111/j.1443- 9573.2006.00243.x
Liu X, Yang X, Zhou G, et al. Gemcitabine-based regional intra-arterial infusion chemotherapy in patients with advanced pancreatic adenocarcinoma. Medicine (Baltimore). 2016;95(11):e3098. https://doi.org/10.1097/ MD.0000000000003098
Cherchenko K, Lukashenko A, Ostapenko Y, et al. Intra-arterial chemotherapy as a clinical option for metastatic colorectal cancer: conversion of inoperable liver metastases to operable illustrated with a clinical case. Exp Oncol. 2024;45(4):515-522. https://doi.org/10.15407/exp-oncology.2023.04.515
Cherchenko K, Lukashenko A, Ostapenko Y, et al. Intra-arterial chemotherapy in metastatic colorectal can- cer: a review of the literature and a clinical case. Clin Oncol. 2022; 3-4(47-48):1-8. https://doi.org/10.32471/ clinicaloncology.2663-466X.49-1.29873 (In Ukrainian).
Boehm LM, Jayakrishnan TT, Miura JT, et al. Comparative effectiveness of hepatic artery based therapies for un- resectable intrahepatic cholangiocarcinoma. J Surg Oncol. 2015;111(2):213-220. https://doi.org/10.1002/jso.23781.
Laface C, Laforgia M, Molinari P, et al. Hepatic arterial infusion of chemotherapy for advanced hepatobiliary can- cers: state of the art. Cancers (Basel). 2021;13(12):3091. https://doi.org/10.3390/cancers13123091
Tao W, Zhao Y, Cai L, Zhu Y. [Distribution of 5-fluorouracil in plasma and pancreatic tissue of rats during the re- gional arterial infusion chemotherapy]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1999;21(5):390-394.
Mitsutsuji M, Suzuki Y, Iwanaga Y, et al. An experimental study on the pharmacokinetics of 5-fluorouracil regional chemotherapy for pancreatic cancer. Ann Surg Oncol. 2003;10(5):546-550. https://doi.org/10.1245/aso.2003.07.018
Tanaka T, Yamamoto K, Sho M, et al. Pharmacokinetic evaluation of pancreatic arterial infusion chemotherapy after unification of the blood supply in an animal model. J Vasc Interv Radiol. 2010;21(1):116-121. https://doi. org/10.1016/j.jvir.2009.09.027
Fu D, Ni Q, Yu X, et al. [Regional intra-arterial infusion chemotherapy for pancreatic cancer: an experimental study]. Zhonghua Yi Xue Za Zhi. 2002;82(6):371-375 (in Chinese)..
van Riel JM, Peters GJ, Mammatas LH, et al. A phase I and pharmacokinetic study of gemcitabine given by 24-h hepatic arterial infusion. Eur J Cancer. 2009;45(14):2519-2527. https://doi.org/10.1016/j.ejca.2009.05.025
Dzodic R, Gomez-Abuin G, Rougier P, et al. Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin admi- nistration: comparative results with cisplatin using a rabbit VX2 tumor model. Anticancer Drugs. 2004;15(6):647- 650. https://doi.org/10.1097/01.cad.0000131684.06390.fe
Guthoff I, Lotspeich E, Fester C, et al. Hepatic artery infusion using oxaliplatin in combination with 5-fluorouracil, folinic acid and mitomycin C: oxaliplatin pharmacokinetics and feasibility. Anticancer Res. 2003;23(6D):5203-5208.
Kakizaki K, Yamauchi H, Takahashi N, et al. [Long-term arterial infusion chemotherapy in unresectable pancreatic cancer]. Gan To Kagaku Ryoho. 1989;16(8 Pt 2):2740-2742 (in Japanese).
Cao Y, Yu D, Wu Y, Zhu W. Regional intra-arterial vs. systemic chemotherapy for the treatment of advanced pan- creatic cancer: a systematic review and meta-analysis. Front Oncol. 2024;14:1197424. https://doi.org/10.3389/ fonc.2024.1197424
Ji Z, Wang Y, Chen X, Wu T. Peripancreatic artery ligation and artery infusion chemotherapy for advanced pancre- atic carcinoma. Chin Med J (Engl). 2003;116(1):89-92.
Liu L, Wang J, Wang X, et al. Effect analysis of arterial gemcitabine chemotherapy for advanced pancreatic cancer.
Chin J Med Comput Imaging. 2007; 202-207. https://doi.org/10.19627/j.cnki.cn31-1700/th.2007.03.016
Jia L, Zheng J, Zhang S, Xie D. A comparative study of gemcitabine arterial infusion chemotherapy and peripheral intravenous chemotherapy in the treatment of advanced pancreatic cancer. Chin J Pancreatic Dis. 2009; 15-17.
Liu H, Li Y, Huang R, Huang X. Clinical observation of regional arterial perfusion of pancreas with GP scheme for advanced pancreatic cancer. Basic Clin Oncol. 2008; 21:479-481.
Qi X, Liu D, Jiang Y. A comparative study of regional chemotherapy and intravenous chemotherapy with GP pro- tocol in the treatment of advanced pancreatic cancer. Chin J Cancer Prev. 2011;18:1556-1558+1562. https://doi. org/10.16073/j.cnki.cjcpt.2011.19.016
Hong GB, Zhou JX, Sun HB, et al. Continuous transarterial infusion chemotherapy with gemcitabine and 5-Fluoro- uracil for advanced pancreatic carcinoma. Asian Pac J Cancer Prev. 2012;13(6):2669-2673. https://doi.org/10.7314/ apjcp.2012.13.6.2669
Endo S, Kawaguchi S, Terada S, Shirane N. Hepatic arterial infusion chemotherapy for liver metastases following standard chemotherapy for pancreatic cancer. Intern Med. 2021;60(2):223-229. https://doi.org/10.2169/internal- medicine.5449-20
Pishvaian M, Zureikat A, Novelli P, et al. The phase 3 study: targeted intra-arterial gemcitabine vs continuation of IV gemcitabine plus nab-paclitaxel following induction with sequential IV gemcitabine plus nab-paclitaxel and radiotherapy for locally advanced pancreatic cancers (TIGeR-PaC) first interim analysis. Presented at: 2023 ESMO World Congress on Gastrointestinal Cancer; June 28 to July 1, 2023; Barcelona, Spain. Abstract LBA-1.
Clinicaltrials.gov. 2025 [cited 2025 Jan 25]. Available from: https://clinicaltrials.gov/study/NCT06196788
Clinicaltrials.gov. 2025 [cited 2025 Jan 25]. Available from: https://clinicaltrials.gov/study/NCT03856658
Clinicaltrials.gov. 2025 [cited 2025 Jan 25]. Available from: https://clinicaltrials.gov/study/NCT06538623
Clinicaltrials.gov. 2025 [cited 2025 Jan 25]. Available from: https://clinicaltrials.gov/study/NCT03755739
Clinicaltrials.gov. 2025 [cited 2025 Jan 25]. Available from: https://clinicaltrials.gov/study/NCT05187338
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
