Arterial chemoembolisation with cisplatin versus epirubicin for hepatocellular carcinoma (ACE 500 study): A multicentre, randomised controlled phase 2/3 trial

Aramaki, Osamu; Takayama, Tadatoshi; Moriguchi, Masamichi; Sakamoto, H; Yodono, Hiraku; Kokudo, Norihiro; Yamanaka, Naoaki; Kawasaki, Seiji; Sasaki, Yo; Kubota, Keiichi; Otsuji, Eigo; Tanaka, Shinji; Matsuyama, Yutaka; Fujii, Masashi

doi:10.1016/j.ejca.2021.08.027

Cited by 16 publications

(8 citation statements)

References 31 publications

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“…Some clinical trials had attempted to compare epirubicin and platinum drugs for TACE and failed to achieve significant superiority. 22 , 23 A study involving 148 patients with unresectable hepatocellular carcinoma showed that TACE with raltitrexed plus liposomal doxorubicin had better clinical efficacy and lower occurrence rates of AEs than TACE with tegafur plus pirarubicin. 24 This may imply that liposomal doxorubicin has benefits when combined with other drugs or therapies.…”

Section: Discussionmentioning

confidence: 99%

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

Shi

Zhang

et al. 2023

Journal of Interventional Medicine

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Section: Discussionmentioning

confidence: 99%

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

Shi

Zhang

et al. 2023

Journal of Interventional Medicine

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“…In regards to single-drug treatment in particular, no specific chemotherapeutic product has demonstrated superiority over another. In a recent study, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227) resulting in a median overall survival (OS) of 2.93 years (95% CI 2.60-3.79) and 2.74 years (95% CI 2.26-3.21), respectively (hazard ratio 0.90 [95% CI 0.71-1.15], p = 0.22) [51]. Similarly, a study comparing cTACE with miriplatin vs. cTACE with epirubicin showed no significant difference in median OS and median times to TACE failure between the two groups, proving once again no superiority of one single drug over another [68].…”

Section: Treatment Deliverymentioning

confidence: 99%

Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE)

Baère

Ronot

Chung

et al. 2022

Cardiovasc Intervent Radiol

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Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) “selectively targetable” and “accessible to supraselective catheterization.” The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5–2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the “drop test.” Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care.

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“…[2][3][4] Epirubicin (EADM) is a frequently used chemotherapeutic agent in HCC. 5 Existing studies have shown that epirubicin inhibits cancer cells by intercalating into DNA strands to inhibit DNA and RNA synthesis. 6,7 However, there is a high probability of adverse reactions (acute dose-limiting hematological toxicity, cardiotoxicity, gastrointestinal stress, weight loss, and alopecia) and resistance to EADM, leading to treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Combined Treatment of Tanshinone I and Epirubicin Revealed Enhanced Inhibition of Hepatocellular Carcinoma by Targeting PI3K/AKT/HIF-1α

Zhao¹,

Lin²,

Cai³

et al. 2022

DDDT

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Background: Epirubicin (EADM) is a common chemotherapeutic agent in hepatocellular carcinoma (HCC). The accumulation of hypoxia-inducible factor-1α (HIF-1α) is an important cause of drug resistance to EADM in HCC. Tanshinone I (Tan I) is an agent with promising anti-cancer effects alone or with other drugs. Some tanshinones mediate HIF-1α regulation via PI3K/AKT. However, the role of Tan I combined with EADM to reduce the resistance of HCC to EADM has not been investigated. Therefore, this study aimed to investigate the combined use of Tan I and EADM in HCC and the underlying mechanism of PI3K/AKT/HIF-1α. Methods: HCC cells were treated with Tan I, EADM, or the combined treatment for 48 hrs. Cell transfection was used to construct HIF-1α overexpression HCC stable cells. Cell viability, colony formation, and flow cytometric assays were used to detect the viability, proliferation, and apoptosis in HCC cells. Synergism between Tan I and EADM were tested by calculating the Bliss synergy score, positive excess over bliss additivism (EOBA), and the combination index (CI). Western blotting analyses were used to detect the levels of β-actin, HIF-1α, PI3K p110α, p-Akt Thr308, Cleaved Caspase-3, and Cleaved Caspase-9. Toxicity parameters were used to evaluate the safety of the combination in mice. The xenograft model of mice was built by HCC stable cell lines, which was administrated with Tan I, EADM, or a combination of them for 8 weeks. Immunohistochemistry staining (IHC) was used to assess tumor apoptosis in mouse models. Results: Hypoxia could upregulate HIF-1α to induce drug resistance in HCC cancer cells. The combination of Tan I and EADM was synergistic. Although Tan I or EADM alone could inhibit HCC cancer cells, the combination of them could further enhance the cytotoxicity and growth inhibition by targeting the PI3K/AKT/HIF-1α signaling pathway. Furthermore, Tan I and EADM synergistically reversed HIF-1α-mediated drug resistance to inhibit HCC. The results of toxicity parameters showed that the combination was safe in mice. Meanwhile, animal models showed that Tan I not only improved the anti-tumor effect of EADM, but also reduced the drug reactions of EADM-induced weight loss. Conclusion: Our results suggested that Tan I could effectively improve the anti-tumor effect of EADM, and synergize EADM to reverse HIF-1α mediated resistance via targeting PI3K/AKT/HIF-1α signaling pathway.

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Arterial chemoembolisation with cisplatin versus epirubicin for hepatocellular carcinoma (ACE 500 study): A multicentre, randomised controlled phase 2/3 trial

Cited by 16 publications

References 31 publications

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE)

Combined Treatment of Tanshinone I and Epirubicin Revealed Enhanced Inhibition of Hepatocellular Carcinoma by Targeting PI3K/AKT/HIF-1α

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