Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma

Naqi, Naeem; Ahmad, Shaharyar; Murad, Sohail; Khattak, Javaid

doi:10.1016/j.hemonc.2013.11.003

Cited by 12 publications

(6 citation statements)

References 12 publications

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“…110 In another phase II study, the efficacy of sorafenib-gemcitabine was evaluated in patients with advanced HCC, and it was considered to be an unsafe therapy as gemcitabine-related thrombocytopenia was followed by sorafenib-related hand-foot skin reaction and anorexia was observed in patients with this combination therapy. 124 Because of these findings, there is an urgent need in clinical trials for sorafenib to be used in combination with different anticancer drug candidates. Tiziana Lifesciences has recently licensed out a new form of CDK inhibitor called as Milciclib.…”

Section: Pembrolizumabmentioning

confidence: 99%

Hepatocellular Carcinoma: Etiology and Current and Future Drugs

Jindal

Thadi

Shailubhai

2019

Journal of Clinical and Experimental Hepatology

202

168

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Hepatocellular carcinoma (HCC) is swiftly increasing in prevalence globally with a high mortality rate. The progression of HCC in patients is induced with advanced fibrosis, mainly cirrhosis, and hepatitis. The absence of proper preventive or curative treatment methods encouraged extensive research against HCC to develop new therapeutic strategies. The Food and Drug Administration-approved Nexavar (sorafenib) is used in the treatment of patients with unresectable HCC. In 2017, Stivarga (regorafenib) and Opdivo (nivolumab) got approved for patients with HCC after being treated with sorafenib, and in 2018, Lenvima (lenvatinib) got approved for patients with unresectable HCC. But, owing to the rapid drug resistance development and toxicities, these treatment options are not completely satisfactory. Therefore, there is an urgent need for new systemic combination therapies that target different signaling mechanisms, thereby decreasing the prospect of cancer cells developing resistance to treatment. In this review, HCC etiology and new therapeutic strategies that include currently approved drugs and other potential candidates of HCC such as Milciclib, palbociclib, galunisertib, ipafricept, and ramucirumab are evaluated.

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Section: Pembrolizumabmentioning

confidence: 99%

Hepatocellular Carcinoma: Etiology and Current and Future Drugs

Jindal

Thadi

Shailubhai

2019

Journal of Clinical and Experimental Hepatology

202

168

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“…In the last 15 years, 38 publications including 2 clinical trials were conducted in Pakistan. Both these trials assessed outcomes of advanced HCC with sorafenib/gemcitabine or arterial infusion of ifosfamide [ 75 , 76 ]. At present, Pakistan is participating in 4 multicenter HCC clinical trials [ 77 ].…”

Section: Research On Hccmentioning

confidence: 99%

Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

Bhatti

Dar

Waheed

et al. 2016

Gastroenterology Research and Practice

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Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level.

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“…To improve its therapeutic efficacy, many sorafenib-based combined modalities have been tested [21,22,23]. However, their overall outcomes are unsatisfactory.…”

Section: Discussionmentioning

confidence: 99%

Combination of Matrine and Sorafenib Decreases the Aggressive Phenotypes of Hepatocellular Carcinoma Cells

Yang

Lin²,

Jin³

et al. 2014

Chemotherapy

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Background: The aim of this study was to determine the effects of matrine (a natural alkaloid) on sorafenib-induced cytotoxicty against hepatocellular carcinoma (HCC) cells, and to explore the molecular mechanisms involved. Methods: HepG2 and Hep3B cells were treated with matrine alone or in combination with sorafenib, and cell viability and apoptosis were assessed. The involvement of micro (mi)RNA-21 in the action of matrine was examined. Results: Matrine significantly augmented the antiproliferative activity of sorafenib in a dose-dependent manner. Matrine significantly increased apoptosis, coupled with enhanced cleavage of caspase-3 and poly (ADP-ribose) polymerase. miRNA-21-overexpressing HCC cells showed a marked decrease in matrine-induced growth suppression and the expression of phosphatase and tensin homolog (PTEN). The suppressive effect of combining matrine and sorafenib was significantly reduced by miRNA-21 overexpression or PTEN inhibition. Conclusion: Matrine in combination with sorafenib leads to increased cytotoxic effects against HCC cells, at least partially, via the suppression of miRNA-21 and the subsequent induction of PTEN.

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Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma

Abstract: The efficacy of sorafenib gemcitabine combination therapy is similar to the sorafenib alone treatment. However, frequent dose adjustments due to gemcitabine-related toxicities, delays, and corrective treatments make this combination therapy unsafe in the treatment of advanced HCC.

Cited by 12 publications

References 12 publications

Hepatocellular Carcinoma: Etiology and Current and Future Drugs

Hepatocellular Carcinoma: Etiology and Current and Future Drugs

Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

Combination of Matrine and Sorafenib Decreases the Aggressive Phenotypes of Hepatocellular Carcinoma Cells

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