Optimal sequence of systemic therapy after sorafenib failure in patients with hepatocellular carcinoma

Han, Sojung; Kim, Do Young

doi:10.3350/cmh.2020.0096

Cited by 5 publications

(3 citation statements)

References 13 publications

(35 reference statements)

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“…A multidisciplinary therapeutic strategy starting from HAIC in the era of the chemo-diversity A multidisciplinary therapeutic strategy is needed in the treatment of advanced HCC [51,52]. The Asian, Korean, and Japanese guideline affirms a multidisciplinary therapeutic strategy combined with systemic treatments and locoregional treatments for advanced HCC, in particular, HCC with PVTT.…”

Section: Haic Complications and Adverse Eventsmentioning

confidence: 99%

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity

Iwamoto¹,

Shimose²,

Shirono³

et al. 2023

Clin Mol Hepatol

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Recently, treatments for unresectable hepatocellular carcinoma (HCC) have undergone remarkable development. Various systemic chemotherapy drugs have been approved and are recommended by clinical guidelines worldwide. Although systemic treatments are effective and contribute to prolonged patient survival, their effects are unsatisfactory for some specific tumor conditions, such as macrovascular invasion. Hepatic arterial infusion chemotherapy (HAIC) is a traditional treatment for advanced HCC. As yet, there is no worldwide consensus recommending HAIC because no high-quality clinical trials have demonstrated its survival benefit. However, clinical evidence is gradually accumulating that shows its survival benefit, and it is recognized as an effective locoregional treatment for advanced HCC. Several HAIC regimens have been reported, including cisplatin monotherapy, cisplatin plus 5-fluorouracil (low-dose FP), lipiodol-suspended FP, and an oxaliplatin-based regimen. We have entered an era of chemo-diversity in the treatment of advanced HCC. This review aimed to clarify the relevance of HAIC in the era of chemo-diversity. We propose a multidisciplinary therapeutic strategy combining locoregional HAIC treatment with sequential drug therapy, with the aim of becoming cancer-free through conversion therapy.

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Section: Haic Complications and Adverse Eventsmentioning

confidence: 99%

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity

Iwamoto¹,

Shimose²,

Shirono³

et al. 2023

Clin Mol Hepatol

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“…In HCC patients with advanced stage, the long-term survival benefit from currently used anticancer treatments is a modest improvement of three months, which is far from satisfactory [ 6 , 7 , 16 , 17 ]. Clinically, there are critical limitations to treat HCC patients: (1) a lack of available drugs after failure of tyrosine kinase inhibitors [ 18 , 19 ]; (2) increasing need of target therapy agents in patients with intermediate stage who showed refractoriness for transarterial chemoembolization or inadequate safety margin of embolized area after TACE [ 12 , 17 , 20 , 21 , 22 , 23 , 24 ]; (3) substantial risk of HCC recurrence even after five years in patients who underwent curative resection [ 25 , 26 , 27 ]; (4) no available drugs for target therapy in patients with decompensated cirrhosis [ 28 ]. Therefore, there is a need to explore novel strategies as alternatives to the currently used drugs in patients with advanced HCC.…”

Section: Introductionmentioning

confidence: 99%

Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1

Kim

Lee

Park

et al. 2021

IJMS

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The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer.

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“…Sorafenib and nivolumab following lenvatinib cost around 2500-4000 USD per month without coverage by the national insurance system in South Korea [23,25]. Patients who experienced serious adverse events, such as hand-foot-skin reaction, hypertension or proteinuria, during lenvatinib treatment might prefer nivolumab rather than sorafenib [26][27][28]. In addition, the different distances between the patients' residences and the two institutes in our study, both of which were located in the South Korean capital of Seoul, might have influenced the choice of second-line agents with different routes of drug administration (1-2 months for oral vs. every 2 weeks for There was no statistical difference between the treatment groups (P = 0.723).…”

Section: Discussionmentioning

confidence: 99%

Sorafenib versus nivolumab after lenvatinib treatment failure in patients with advanced hepatocellular carcinoma

Kim

Lee

et al. 2022

European Journal of Gastroenterology &Amp; Hepatology

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Background and aim An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC. Methods Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020. ResultsThe median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively (P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P < 0.05). Conclusions Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.

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Optimal sequence of systemic therapy after sorafenib failure in patients with hepatocellular carcinoma

Cited by 5 publications

References 13 publications

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity

Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1

Sorafenib versus nivolumab after lenvatinib treatment failure in patients with advanced hepatocellular carcinoma

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