Efficacy of Hepatic Arterial Infusion Chemotherapy Using 5-Fluorouracil and Systemic Pegylated Interferon α-2b for Advanced Intrahepatic Cholangiocarcinoma

Kasai, Kazuhiro; Kooka, Yohei; Suzuki, Yuji; Suzuki, Akiko; Oikawa, Takashi; Ushio, Akira; Kasai, Yukiho; Sawara, Kei; Miyamoto, Yukio; Oikawa, Kanta; Takikawa, Yasuhiro

doi:10.1245/s10434-014-3766-7

Cited by 24 publications

(31 citation statements)

References 44 publications

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“…Of note, 16 of these studies assessed the safety and efficacy of FDA-approved cytokines (i.e., G-CSF, GM-CSF, IFN-a2a, IFN-a2b and IL-2) as off-label immunostimulatory interventions, [98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113] while only one trial tested the clinical profile of a hitherto experimental cytokine (i.e., IL-15). 114 The safety and efficacy of G-CSF have been assessed in 11 breast carcinoma patients, who were treated with subcutaneous G-CSF in combination with 5-fluorouracil (5-FU), epirubicin, cyclophosphamide and paclitaxel (NCT02225652).…”

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

“…98 The safety and efficacy of IFN-a2a and IFN-a2b have been evaluated in (1) five cohorts of 791, 365, 53, 51 and 40 subjects with advanced RCC, who received IFN-a2a in combination with the FDA-approved tumor-targeting antibody bevacizumab (which neutralizes vascular endothelial growth factor A, VEGFA) [121][122][123] (NCT00719264), along with the multitarget tyrosine kinase inhibitor sorafenib (UMIN000002466), 124,125 in the context of a multimodal treatment involving potentially immunogenic chemotherapy plus bevacizumab i.v. and low dose IL-2 s.c., [126][127][128] ; or optionally combined with a trophoblast glycoprotein (TPBG)-redirected variant of staphylococcal enterotoxin A (naptumomab estafenatox); 100,105,108,113,129 (2) 313 patients with symptomatic indolent B-cell lymphoma, receiving IFN-a2a in combination with the CD20-targeting mAb rituximab 130,131 99 Cumulatively, these studies confirm that IFNa2a and IFN-a2b can be safely administered to cancer patients as off-label indications. IFN-a2a improved the clinical efficacy of sorafenib-based chemotherapy for advanced RCC, 113 but failed to do so better than the mechanistic target of rapamycin (MTOR) inhibitors everolimus or temsirolimus 132,133 (although it was associated with a lower incidence of side effects) in patients with metastatic RCC co-treated with bevacizumab, 108,129 as it failed to ameliorate the therapeutic profile of rituximab in indolent B-cell lymphoma patients.…”

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

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Trial Watch—Immunostimulation with cytokines in cancer therapy

Vacchelli¹,

Aranda

Bloy³

et al. 2015

OncoImmunology

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During the past decade, great efforts have been dedicated to the development of clinically relevant interventions that would trigger potent (and hence potentially curative) anticancer immune responses. Indeed, developing neoplasms normally establish local and systemic immunosuppressive networks that inhibit tumor-targeting immune effector cells, be them natural or elicited by (immuno)therapy. One possible approach to boost anticancer immunity consists in the (generally systemic) administration of recombinant immunostimulatory cytokines. In a limited number of oncological indications, immunostimulatory cytokines mediate clinical activity as standalone immunotherapeutic interventions. Most often, however, immunostimulatory cytokines are employed as immunological adjuvants, i.e., to unleash the immunogenic potential of other immunotherapeutic agents, like tumor-targeting vaccines and checkpoint blockers. Here, we discuss recent preclinical and clinical advances in the use of some cytokines as immunostimulatory agents in oncological indications.

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Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

Trial Watch—Immunostimulation with cytokines in cancer therapy

Vacchelli¹,

Aranda

Bloy³

et al. 2015

OncoImmunology

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“…Hepatic arterial infusion chemotherapy (HAIC)-injecting chemotherapeutic agents into the hepatic artery without embolization-reduces the systemic side effects seen with systemic chemotherapy ( 13 ). Previous studies have illustrated that HAIC is a promising option for advanced ICC and has shown higher tumor control rates than systemic chemotherapy ( 14 ). Chemotherapy with hepatic intraarterial epirubicin and cisplatin combined with systemic 5-fluorouracil (5-FU) was used in patients with unresectable ICC, and the objective response rate and median survival time were 36% and 15.4 months, respectively ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma

Cai

Zhao

et al. 2021

Front. Oncol.

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BackgroundIntrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment.MethodsBetween March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups.ResultsICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort.ConclusionsHAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.

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“…Combination of weekly pegylated interferon α-2b and intra-arterial infusion of 5-FU has been shown to confer 1-year survival rate of 54% and median survival of almost 15 months in a recent study. 145 The recent phase I/II study from Japan showed that gemcitabine infusion was associated with tumor response of 8%, with neutropenia being the major side effect of this treatment. HAI has been reported with 5-FU-based regimens and has shown effectiveness, but large trials are lacking.…”

Section: Hepatic Artery-based Therapiesmentioning

confidence: 99%

Comprehensive management of cholangiocarcinoma: Part II. Treatment

Papafragkakis

Lee

2017

Int J Gastrointest Interv

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Cholangioarcinoma is a rare but dreadful malignancy which poses much difficulties in the management. If detected early with only localized disease, curative resection is possible. However, most patients present in the late stages of the disease, which are managed with endoscopic biliary drainage and/or chemoradiation. Liver transplantation offers a possibility for cure in the distal and the perihilar tumors for selected candidates. Local treatments, such as hepatic artery-based therapies, brachytherapy, and photodynamic therapy, may offer some benefit in cases of the advanced disease. In this review, we will assess the role of preoperative biliary drainage, how best to drain biliary obstruction, and the intricate details of various treatments that are currently available. Management of Cholangiocarcinoma Preoperative biliary drainagePreoperative biliary drainage (PBD) is achieved with endoscopic or percutaneous approach. The topic is controversial and the review of the literature revealed conflicting results. PBD of the future remnant hepatic lobe is supposed to decrease hepatic dysfunction and liver failure postoperatively.1 The meta-analysis found no difference in mortality between patients with and without PBD and the authors advised that such procedure should not be performed routinely.2 Another meta-analysis of almost 5,000 patients with distal obstruction (425 with distal cholangiocarcinoma [DCC]) did not find any evidence that PBD (without distinguishing between endoscopic or percutaneous approach) increases morbidity or mortality. However it was associated with significant bacterial infection of the bile and possibly adverse outcomes after surgery.3 Other studies showed that PBD reduced jaundice, which positively affected outcomes, but not survival, and that it might be associated with more intraoperative blood loss, but less reoperation rates compared to non-drained cases. 4,5 The prospective randomized study of almost 200 patients with cancer of the head of the pancreas demonstrated that PBD was associated with more non-surgical adverse events compared to those managed only with surgery (46% vs 2%, respectively). Surgical adverse events were also more in the PBD group (47% vs 37%). The high incidence of cholangitis in those treated with PBD may be associated with the long lag time between PBD and surgery (5 weeks) and the high occlusion rate of plastic stents (PSs) (15%), prompting other authors to suggest that use of short, self-expandable metal stents (SEMS) may result in better outcomes for distal bile duct strictures. In accordance with other studies, there was no effect of PBD on mortality.6,7 In perihilar cholangiocarcinoma (PCC), the systematic review of 700 patients with and without PBD suggested that there is higher incidence of postoperative infections (18%-52% vs 0%-27%) and overall adverse events (36%-100% vs 29%-72%) in the PBD compared to the non-PBD group. There was no difference in mortality in the two groups. 8 Other studies favor the use of PBD in the preoperative management of PCC. ...

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Efficacy of Hepatic Arterial Infusion Chemotherapy Using 5-Fluorouracil and Systemic Pegylated Interferon α-2b for Advanced Intrahepatic Cholangiocarcinoma

Cited by 24 publications

References 44 publications

Trial Watch—Immunostimulation with cytokines in cancer therapy

Trial Watch—Immunostimulation with cytokines in cancer therapy

Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma

Comprehensive management of cholangiocarcinoma: Part II. Treatment

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