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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| Format: | Article |
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MDPI AG
2015-12-01
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| Series: | Diseases |
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| Online Access: | http://www.mdpi.com/2079-9721/3/4/360 |
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| author | Masafumi Ikeda Shuichi Mitsunaga Izumi Ohno Yusuke Hashimoto Hideaki Takahashi Kazuo Watanabe Kumiko Umemoto Takuji Okusaka |
| author_facet | Masafumi Ikeda Shuichi Mitsunaga Izumi Ohno Yusuke Hashimoto Hideaki Takahashi Kazuo Watanabe Kumiko Umemoto Takuji Okusaka |
| author_sort | Masafumi Ikeda |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T01:50:13Z |
| format | Article |
| id | doaj.art-a3efcc0065074219afc4a6a1c2905783 |
| institution | Directory Open Access Journal |
| issn | 2079-9721 |
| language | English |
| last_indexed | 2024-12-13T01:50:13Z |
| publishDate | 2015-12-01 |
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| record_format | Article |
| series | Diseases |
| spelling | doaj.art-a3efcc0065074219afc4a6a1c29057832022-12-22T00:03:33ZengMDPI AGDiseases2079-97212015-12-013436038110.3390/diseases3040360diseases3040360Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and FutureMasafumi Ikeda0Shuichi Mitsunaga1Izumi Ohno2Yusuke Hashimoto3Hideaki Takahashi4Kazuo Watanabe5Kumiko Umemoto6Takuji Okusaka7Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, JapanDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, JapanDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, JapanDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, JapanDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, JapanDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, JapanDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, JapanDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, JapanSystemic 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.http://www.mdpi.com/2079-9721/3/4/360hepatocellular carcinomachemotherapysorafenibimmune-oncologic agentsindividualized treatment |
| spellingShingle | Masafumi Ikeda Shuichi Mitsunaga Izumi Ohno Yusuke Hashimoto Hideaki Takahashi Kazuo Watanabe Kumiko Umemoto Takuji Okusaka Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future Diseases hepatocellular carcinoma chemotherapy sorafenib immune-oncologic agents individualized treatment |
| 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 | hepatocellular carcinoma chemotherapy sorafenib immune-oncologic agents individualized treatment |
| url | http://www.mdpi.com/2079-9721/3/4/360 |
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