Efficacy and tolerability of Sorafenib plus metronomic chemotherapy S-1 for advanced hepatocellular carcinoma in preclinical and clinical assessments

•Sorafenib plus MC S-1 chemotherapy can be safely used in patients with advanced HCC.•Combination of the metronomic chemotherapy enhanced anti-angiogenic effects, leading a stronger tumor hypoxic environment.•Strong intra tumoral hypoxia increased tumor cell apoptosis and reduced tumor cells prolife...

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Published in:Translational oncology 2021-11, Vol.14 (11), p.101201-101201, Article 101201
Main Authors: Suzuki, Hiroyuki, Iwamoto, Hideki, Nakano, Masahito, Nakamura, Toru, Masuda, Atsutaka, Sakaue, Takahiko, Tanaka, Toshimitsu, Nakano, Dan, Kuromatsu, Ryoko, Niizeki, Takashi, Okamura, Shusuke, Shimose, Shigeo, Shirono, Tomotake, Noda, Yu, Kamachi, Naoki, Yano, Hirohisa, Kawaguchi, Atsushi, Koga, Hironori, Torimura, Takuji
Format: Article
Language:English
Subjects:
Combination chemotherapy
Hepatocellular carcinoma
Metronomic chemotherapy
Original Research
S-1
Sorafenib
STAM mouse
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Summary:•Sorafenib plus MC S-1 chemotherapy can be safely used in patients with advanced HCC.•Combination of the metronomic chemotherapy enhanced anti-angiogenic effects, leading a stronger tumor hypoxic environment.•Strong intra tumoral hypoxia increased tumor cell apoptosis and reduced tumor cells proliferation. Although sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus sorafenib. Antitumor effects and toxicity of this combination were tested with HAK-1B xenograft and spontaneous HCC mouse models, and a prospective pilot study was performed to compare therapeutic effects and safety between sorafenib plus MC S-1 for 12 advanced HCC cases and the historical control of 363 sorafenib-treated advanced HCC patients at our hospital from July 2011 to June 2015. In mice, the combination chemotherapy enhanced anti-angiogenic effects, resulting in a stronger tumor hypoxic environment and increased tumor cell apoptosis. Clinically, the objective response rate of the combination chemotherapy was higher than that of sorafenib mono therapy (16.7%; 2/12 vs 5.2%; 19/363, p 
ISSN:1936-5233
1936-5233
DOI:10.1016/j.tranon.2021.101201