Capecitabine in advanced hepatocellular carcinoma

Murer, F.; Pozzan, C.; Peserico, Giulia; Farinati, Fabio

doi:10.1016/j.dld.2016.06.037

Cited by 7 publications

(10 citation statements)

References 5 publications

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“…Another indication of MC efficacy is provided by the longlasting objective TR reported in three patients with an unresectable HCC (Brandi et al 2010;Marinelli et al 2013). On the other hand, a brief report by Murer et al reported a short survival (mean: 6.3 months) in 25 HCC patients undergoing MC as both first-and second-line chemotherapy, with no significant differences between the two groups (Murer et al 2016). This poorer survival compared with that of our and previous studies (Brandi et al 2013;Granito et al 2015) could depend on the worse liver function and performance status of Murer's patients.…”

Section: Discussioncontrasting

confidence: 53%

“…Capecitabine, a prodrug of 5-fluorouracil (5-FU) metabolized to the active drug preferentially in liver and tumor tissue by thymidine phosphorylase (Walko and Lindley 2005), has been tested as first-and second-line treatment for HCC by some studies, using either the conventional or metronomic approach (Patt et al 2004;Lee et al 2009;Farrag 2012;He et al 2013;Abdel-Rahman et al 2013;Brandi et al 2013;Granito et al 2015;Murer et al 2016;Casadei Gardini et al 2017). The obtained results are sparse and rather conflicting, and only one of these studies compared capecitabine with best supportive care (BSC) in the setting of second-line therapy (Casadei Gardini et al 2017).…”

Section: Introductionmentioning

confidence: 99%

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Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation

Trevisani

Brandi

Garuti

et al. 2017

J Cancer Res Clin Oncol

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Section: Discussioncontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation

Trevisani

Brandi

Garuti

et al. 2017

J Cancer Res Clin Oncol

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“…Capecitabine, a prodrug of 5FU, is used as a first- and second-line drugs for HCC treatment by several clinical trials ( Murer et al, 2016 ; Casadei Gardini et al, 2017 ). The in vivo antitumor activity of capecitabine was stronger than that of 5FU in H22 cell-bearing Kunming (KM) mice transplant model (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…Capecitabine has been tested as first- and second-line treatments for HCC by some studies ( Murer et al, 2016 ; Casadei Gardini et al, 2017 ), and its antitumor activity was higher than that of 5FU in the mice transplant model. In the present assay, the capecitabine dosage was the maximum endurable dosage, while BC-02 was used at a much lower dosage.…”

Section: Discussionmentioning

confidence: 99%

CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents

Zhang

Fang

et al. 2018

Front. Pharmacol.

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Multidrug resistance (MDR) of hepatocellular carcinoma is a serious problem. Although CD13 is a biomarker in human liver cancer stem cells, the relationship between CD13 and MDR remains uncertain. This study uses liver cancer cell model to understand the role of CD13 in enhancing the cytotoxic effect of chemotherapy agents. Cytotoxic agents can induce CD13 expression. CD13 inhibitor, bestatin, enhances the antitumor effect of cytotoxic agents. Meanwhile, CD13-targeting siRNA and neutralizing antibody can enhance the cytotoxic effect of 5-fluorouracil (5FU). CD13 overexpression increases cell survival upon cytotoxic agents treatment, while the knockdown of CD13 causes hypersensitivity of cells to cytotoxic agents treatment. Mechanistically, the inhibition of CD13 leads to the increase of cellular reactive oxygen species (ROS). BC-02 is a novel mutual prodrug (hybrid drug) of bestatin and 5FU. Notably, BC-02 can inhibit cellular activity in both parental and drug-resistant cells, accompanied with significantly increased ROS level. Moreover, the survival time of Kunming mice bearing H22 cells under BC-02 treatment is comparable to the capecitabine treatment at maximum dosage. These data implicate a therapeutic method to reverse MDR by targeting CD13, and indicate that BC-02 is a potent antitumor compound.

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“…Capecitabine, an oral 5‐fluorouracil prodrug approved for the treatment of metastatic colorectal and breast cancer, has been used off label to treat HCC and showed modest activity before any anti‐HCC drugs were approved [21–25]. Studies also showed that capecitabine plus bevacizumab, or capecitabine plus bevacizumab/oxaliplatin in advanced HCC, were also effective and tolerable [26, 27]. The most common side effects associated with capecitabine are myelosuppression and skin toxicity, and the most limiting side effect is severe gastrointestinal (GI) toxicity.…”

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confidence: 99%

A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma

et al. 2020

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Lessons Learned A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies. This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC. Background This study aimed to evaluate efficacy and safety of capecitabine combined with a PHY906 (a pharmaceutical‐grade formulation of four traditional Chinese herbs) in the treatment of advanced hepatocellular carcinoma (HCC) in Asian patients who were positive for hepatitis B virus (HBV). Methods This study was an open‐label, phase II safety and efficacy clinical trial of PHY906 and capecitabine in patients with advanced HCC. Patients received 750 mg/m2 capecitabine b.i.d. 14 days plus 800 mg of PHY906 b.i.d. on days 1–4 and days 8–11 every 21‐day cycle. The primary endpoint was 6‐month survival rate, and secondary endpoints were progression‐free survival, overall survival, disease control rate, and safety. Results Thirty‐nine subjects completed the study with a 46.2% stable disease rate. The median progression‐free survival was 1.5 months, and median overall survival (mOS) was 6 months with a 51.3% 6‐month survival rate. The most common adverse events included lower hemoglobin, diarrhea, pain, abdomen (not otherwise specified), fatigue, increased aspartate aminotransferase, and bilirubin. Patients who (a) had not received previous chemotherapies or targeted therapy or (b) had lower starting alpha‐fetoprotein (AFP) levels or (c) had HBV infection showed better clinical outcome. Conclusion Our data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC.

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Capecitabine in advanced hepatocellular carcinoma

Cited by 7 publications

References 5 publications

Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation

Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation

CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents

A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma

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