Randomised clinical trial: comparison of two everolimus dosing schedules in patients with advanced hepatocellular carcinoma

Shiah, Her Shyong; Chen, Chiung Yu; Dai, Chia Yen; Hsiao, Chin‐Fu; Lin, Yih Jyh; Su, Wu Chou; Chang, Jang Yang; Whang‐Peng, Jacqueline; Lin, Pin Wen; Huang, Jin; Chen, Li Tzong

doi:10.1111/apt.12132

Cited by 60 publications

(43 citation statements)

References 42 publications

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“…Data from phase 1 and 2 studies showed a stabilization of HCC progression with everolimus (72,73). As yet there are no clinical studies to establish its true role.…”

Section: Mammalian Target Of Rapamycin Inhibitors (Mtor)mentioning

confidence: 99%

Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence

Khorsandi¹,

Heaton²

2016

Transl. Gastroenterol. Hepatol.

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“…Data from phase 1 and 2 studies showed a stabilization of HCC progression with everolimus (72,73). As yet there are no clinical studies to establish its true role.…”

Section: Mammalian Target Of Rapamycin Inhibitors (Mtor)mentioning

confidence: 99%

Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence

Khorsandi¹,

Heaton²

2016

Transl. Gastroenterol. Hepatol.

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“…Data from clinical trials on a variety of molecular targeted therapies for advanced HCC are shown in table 1[3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56]. …”

Section: Clinical Trials Of Molecular Targeted Therapy For Advanced Hccmentioning

confidence: 99%

“…The recommended phase II dose of everolimus was 7.5 or 10 mg per day for monotherapy in HCC patients [28,29]. A phase III, randomized, placebo-controlled trial testing the efficacy of everolimus 7.5 mg po qd after sorafenib failure has completed patient recruitment, and the results will be available by the end of 2013.…”

Section: Clinical Trials Of Molecular Targeted Therapy For Advanced Hccmentioning

confidence: 99%

Clinical Trials in Hepatocellular Carcinoma: An Update

et al. 2013

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The success of sorafenib has spurred an explosive increase of clinical trials testing novel molecular targets and other agents in the treatment of hepatocellular carcinoma (HCC). The paradigm of the studies has been characterized by three noticeable changes. First, the molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for advanced HCC treatment. Agents targeting EGFR, FGFR, PI3K/Akt/mTOR, TGF-β, c-Met, MEK, IGF signaling, and histone deacetylase have been actively explored. Second, the target indication has shifted from advanced stage to early or intermediate stages of disease. The feasibility of combining locoregional therapies and targeted agents, and the use of novel agents after curative treatments are currently under active investigation. Finally, the therapeutic strategy has shifted from monotherapy to combination targeted therapy. We aim to provide a comprehensive overview of newly disclosed and ongoing clinical trials for the treatment of HCC.

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“…Currently, everolimus has proven anticancer activity in advanced renal cell carcinoma following VEGFr-TKIs [43], in advanced, progressive neuroendocrine tumors [44], and, in combination with exemestane, in advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on prior hormonal therapy [45]. Data regarding the safety and efficacy of everolimus in HCC come from two prospective studies [46,47]. In a phase I/II trial conducted in 28 patients with advanced HCC, 20 (71%) of whom had received previous systemic therapy, no dose-limiting toxicities were experienced and everolimus was generally well tolerated at a dose of 10 mg/day [46].…”

Section: Mtor Inhibition In Unresectable Advanced Hccmentioning

confidence: 99%

“…A phase I dose-finding study on everolimus for advanced HCC evaluated both daily (n =21) and weekly (n =18) dosing schedules [47]. Based on the observed dose-limiting toxicities of hyperbilirubinemia, alanine aminotransferase elevation, thrombocytopenia, infection, diarrhea, rectal bleeding, and cardiac ischemia, the maximum tolerated doses were determined to be 70 mg/week and 7.5 mg/day.…”

Section: Mtor Inhibition In Unresectable Advanced Hccmentioning

confidence: 99%

Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition

Finn

2012

Liver Cancer

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Hepatocellular carcinoma (HCC) is a common cancer that has the third highest cancer-related mortality rate worldwide. Although potentially curable by transplantation if detected early, the majority of cases are diagnosed at an advanced stage of disease for which limited treatment options are available. The only proven systemic therapy for advanced HCC is sorafenib, a multi-kinase inhibitor that has demonstrated modest efficacy and reasonable tolerability in patients with advanced HCC. Five years after the approval of sorafenib, no other agent has been proven to be beneficial in the first- or second-line setting in advanced HCC. While molecular studies have highlighted various potential targets in HCC, the mammalian target of rapamycin (mTOR) has emerged as an exciting target for cancer therapy including HCC. Laboratory data have linked the phosphatidylinositol 3-kinase/AKT/mTOR axis to various oncogenic processes, including survival and angiogenesis. Historically, mTOR inhibitors have been used for their immunosuppressive properties, but more recently they have been approved as anticancer agents. Retrospective HCC studies suggest that the inclusion of mTOR inhibition as part of an immunosuppressant regimen after transplantation may reduce HCC recurrence compared with other immunosuppressive agents such as calcineurin inhibitors. More recently, single-arm, phase I/II studies have shown that mTOR inhibitors also have activity as monotherapy in cases of recurrent HCC or de novo advanced HCC. This article will review the rationale for targeting the mTOR pathway in HCC, and the currently available clinical data supporting its development for HCC.

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Randomised clinical trial: comparison of two everolimus dosing schedules in patients with advanced hepatocellular carcinoma

Abstract: SUMMARY BackgroundDeregulation of mammalian target of rapamycin (mTOR) signalling is common in human hepatocellular carcinoma (HCC).

Cited by 60 publications

References 42 publications

Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence

Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence

Clinical Trials in Hepatocellular Carcinoma: An Update

Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition

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