Sustained-hepatic arterial infusion of oxaliplatin: pharmacokinetic advantages over hepatic arterial infusion using a preclinical animal tumour model

Abstract Objective To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). Methods We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. Results Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1–9.3) than in the control group (4.3 months, 95% CI: 3.6–5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1–16.5; control: 8.5 months, 95% CI: 7.6–9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. Conclusions Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. Key Points • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.

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The impact of sorafenib in combination with intermittent hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma with major vascular invasion

Cancer Investigation ◽

10.1080/07357907.2021.1952594 ◽

2021 ◽

pp. 1-28

Author(s):

Masaki Kaibori ◽

Hideyuki Matsushima ◽

Morihiko Ishizaki ◽

Hisashi Kosaka ◽

Kosuke Matsui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Vascular Invasion ◽

Hepatic Arterial Infusion ◽

Hepatic Arterial Infusion Chemotherapy ◽

Arterial Infusion ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy ◽

Unresectable Hepatocellular Carcinoma ◽

The Impact

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Clinical Benefits of Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma

Applied Sciences ◽

10.3390/app11041882 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1882

Author(s):

Takahiro Yamasaki ◽

Issei Saeki ◽

Yurika Kotoh-Yamauchi ◽

Ryo Sasaki ◽

Norikazu Tanabe ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Vascular Invasion ◽

Hepatic Arterial Infusion ◽

Hepatic Arterial Infusion Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy ◽

Recent Success ◽

Clinical Benefits

Recent success of systemic therapeutic agents, including combination immunotherapy, could promote a change in the treatment strategy in patients with advanced hepatocellular carcinoma (HCC). Although hepatic arterial infusion chemotherapy (HAIC) is a treatment option for advanced HCC in Japan, it is not recommended by other guidelines. We discuss the clinical benefits of HAIC compared to sorafenib. The clinical benefits of HAIC are as follows: (1) even a patient with Child–Pugh B HCC (7 or 8 points) is a candidate for HAIC (2) Child–Pugh scores barely decline with the use of HAIC compared with sorafenib (3) HAIC is highly effective in patients with vascular invasion compared with sorafenib; and (4) survival in patients receiving HAIC may not be associated with skeletal muscle volume. In contrast, the disadvantages are problems related with the reservoir system. HAIC has clinical benefits in a subpopulation of patients without extrahepatic metastasis with Child–Pugh A HCC and vascular invasion (especially primary branch invasion or main portal vein invasion) or with Child–Pugh B HCC.

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Identification of the Response-Related Biomarker of Bimonthly Hepatic Arterial Infusion Chemotherapy

Journal of Clinical Medicine ◽

10.3390/jcm10040629 ◽

2021 ◽

Vol 10 (4) ◽

pp. 629

Author(s):

Kei Moriya ◽

Tadashi Namisaki ◽

Hiroaki Takaya ◽

Kosuke Kaji ◽

Hideto Kawaratani ◽

...

Keyword(s):

Hepatic Arterial Infusion ◽

Progression Free Survival ◽

Serum Levels ◽

Hepatic Arterial Infusion Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Term Survival ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy ◽

Molecularly Targeted Agents

Despite the availability of molecularly targeted agents for advanced hepatocellular carcinoma (aHCC), these are limited to compensated cirrhotic patients, and concerns about decreased hepatic functional reserve (HFR) and unknown adverse events, which may affect long-term survival, remain unaddressed. In this study, we enrolled 96 aHCC patients treated with bimonthly hepatic arterial infusion chemotherapy (B-HAIC) with cisplatin or sorafenib monotherapy (oral sorafenib 400 mg twice daily) not only to demonstrate its efficacy and significance but also to indicate preferable candidates by setting a response-related biomarker. Differences in treatment had no significant effect on overall survival (OS). The response rate in patients treated with B-HAIC was relatively higher than those treated with sorafenib. HFR was well maintained over the treatment course with B-HAIC, while it was significantly impaired with sorafenib. By employing multivariate analysis, we found negative trends between progression-free survival (PFS) periods and serum levels of alpha fetoprotein as well as des-gamma-carboxy prothrombin (DCP). In addition, a logistic regression analysis of the relationship between serum DCP levels and PFS periods over 420 days (14 months) showed that the PFS periods of patients with higher DCP was significantly shorter than those of patients with lower DCP (p = 0.02). Subsequently, the present study demonstrated the efficacy and safety of B-HAIC and identified a predictor of unpreferable patients. Based on these results, B-HAIC might be an alternative treatment after the implementation of new molecularly targeted therapies.

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