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Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future

Systemic chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). Before the introduction of sorafenib, cytotoxic agents, hormonal therapies, or many combinations of these were the mainly used modalities for systemic chemotherapy of advanced HCC. Ho...

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Autores principales: Ikeda, Masafumi, Mitsunaga, Shuichi, Ohno, Izumi, Hashimoto, Yusuke, Takahashi, Hideaki, Watanabe, Kazuo, Umemoto, Kumiko, Okusaka, Takuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548259/
https://www.ncbi.nlm.nih.gov/pubmed/28943630
http://dx.doi.org/10.3390/diseases3040360
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author Ikeda, Masafumi
Mitsunaga, Shuichi
Ohno, Izumi
Hashimoto, Yusuke
Takahashi, Hideaki
Watanabe, Kazuo
Umemoto, Kumiko
Okusaka, Takuji
author_facet Ikeda, Masafumi
Mitsunaga, Shuichi
Ohno, Izumi
Hashimoto, Yusuke
Takahashi, Hideaki
Watanabe, Kazuo
Umemoto, Kumiko
Okusaka, Takuji
author_sort Ikeda, Masafumi
collection PubMed
description Systemic chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). Before the introduction of sorafenib, cytotoxic agents, hormonal therapies, or many combinations of these were the mainly used modalities for systemic chemotherapy of advanced HCC. However, such regimens were of only limited value in clinical practice, because some randomized controlled studies comparing promising regimens with no treatment or doxorubicin alone failed to show any overall survival advantage. In two pivotal phase III placebo-controlled studies, the SHARP trial and the Asia-Pacific trial, sorafenib was demonstrated to significantly delay the time to progression and the overall survival time in patients with advanced HCC. Therefore, sorafenib therapy has come to be acknowledged as a standard therapy for advanced HCC worldwide. After the introduction of sorafenib, a number of phase III trials of various molecular-targeted agents vs. sorafenib as first-line chemotherapy and of various molecular-targeted agents vs. placebo as second-line chemotherapy have been conducted to determine if any of these agents could offer a survival benefit, however, none of the agents examined so far has been demonstrated to provide any survival benefit over sorafenib or placebo. Recently, favorable treatment efficacies have been reported in some clinical trials of molecular-targeted agents in the biomarker-enriched population. Development of individualized cancer treatments using molecular-targeted agents based on the results of genome-sequencing is aggressively ongoing. Furthermore, immune-oncologic agents, such as anti-CTLA-4 antibody and anti-PD-1/PD-L1 antibody, have been reported to provide promising outcomes. Thus, various novel systemic chemotherapeutic agents are currently under development, and further improvements in the treatment outcomes are expected.
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spelling pubmed-55482592017-09-12 Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future Ikeda, Masafumi Mitsunaga, Shuichi Ohno, Izumi Hashimoto, Yusuke Takahashi, Hideaki Watanabe, Kazuo Umemoto, Kumiko Okusaka, Takuji Diseases Review Systemic chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). Before the introduction of sorafenib, cytotoxic agents, hormonal therapies, or many combinations of these were the mainly used modalities for systemic chemotherapy of advanced HCC. However, such regimens were of only limited value in clinical practice, because some randomized controlled studies comparing promising regimens with no treatment or doxorubicin alone failed to show any overall survival advantage. In two pivotal phase III placebo-controlled studies, the SHARP trial and the Asia-Pacific trial, sorafenib was demonstrated to significantly delay the time to progression and the overall survival time in patients with advanced HCC. Therefore, sorafenib therapy has come to be acknowledged as a standard therapy for advanced HCC worldwide. After the introduction of sorafenib, a number of phase III trials of various molecular-targeted agents vs. sorafenib as first-line chemotherapy and of various molecular-targeted agents vs. placebo as second-line chemotherapy have been conducted to determine if any of these agents could offer a survival benefit, however, none of the agents examined so far has been demonstrated to provide any survival benefit over sorafenib or placebo. Recently, favorable treatment efficacies have been reported in some clinical trials of molecular-targeted agents in the biomarker-enriched population. Development of individualized cancer treatments using molecular-targeted agents based on the results of genome-sequencing is aggressively ongoing. Furthermore, immune-oncologic agents, such as anti-CTLA-4 antibody and anti-PD-1/PD-L1 antibody, have been reported to provide promising outcomes. Thus, various novel systemic chemotherapeutic agents are currently under development, and further improvements in the treatment outcomes are expected. MDPI 2015-12-01 /pmc/articles/PMC5548259/ /pubmed/28943630 http://dx.doi.org/10.3390/diseases3040360 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ikeda, Masafumi
Mitsunaga, Shuichi
Ohno, Izumi
Hashimoto, Yusuke
Takahashi, Hideaki
Watanabe, Kazuo
Umemoto, Kumiko
Okusaka, Takuji
Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
title Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
title_full Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
title_fullStr Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
title_full_unstemmed Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
title_short Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
title_sort systemic chemotherapy for advanced hepatocellular carcinoma: past, present, and future
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548259/
https://www.ncbi.nlm.nih.gov/pubmed/28943630
http://dx.doi.org/10.3390/diseases3040360
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