Activity and safety of pegylated liposomal doxorubicin, 5-fluorouracil and folinic acid in inoperable hepatocellular carcinoma: A phase II study

Lorenzo, Giuseppe Di; Rea, Antonio; Carlomagno, Chiara; Pepe, Stefano; Palmieri, Giovannella; Labianca, Roberto; Chirianni, Antonio; Stefano, Alfonso De; Esposito, Vincenzo; Placido, Sabino De; Montesarchio, Vincenzo

doi:10.3748/wjg.v13.i48.6553

Cited by 5 publications

(5 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, toxicities related to the drug may be exaggerated due to the existence of a liver disease [21,22]. Other options such as surgery and transplantation are considered curative, but are only available in patients with early hepatocellular carcinoma and are rarely option for patients with metastatic disease due to the advanced nature at presentation.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma

Cohn¹,

Myers²,

Mamus³

et al. 2008

Invest New Drugs

View full text Add to dashboard Cite

Pemetrexed has demonstrated activity in hepatocellular carcinoma (HCC) cell lines, and has a manageable toxicity profile in clinical trials, suggesting its potential as a treatment for HCC patients. A multicenter, Phase II community-based study was conducted to assess the response rate and toxicity profile of single-agent pemetrexed in first-line patients with advanced or metastatic HCC. Patients premedicated with folic acid, vitamin B(12), and dexamethasone were administered pemetrexed 600 mg/m(2) IV on day 1 of each 21-day cycle until disease progression. This nonrandomized study employed Simon's 2-stage design, enrolling 21 eligible patients in the first stage, stopping accrual if < or =2 responders were observed. Responses were four stable disease, 14 progressive disease, and three not evaluable: two had early toxicities (renal/liver failure, sepsis) and one was noncompliant. The most common grade 3 hematological toxicities were neutropenia 6 of 21 (29%) and thrombocytopenia 3 of 21 (14%); with no grade 4 toxicities. Thirteen patients died on-study: 12 PD and one liver failure; none were drug-related. The median survival was 5.2 months (range, <1-12.2). The planned second stage was cancelled, and the trial was closed owing to lack of response. While pemetrexed was tolerated in this patient population, it was not active.

show abstract

Section: Discussionmentioning

confidence: 99%

A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma

Cohn¹,

Myers²,

Mamus³

et al. 2008

Invest New Drugs

View full text Add to dashboard Cite

show abstract

“…5-FU is one of the most common anticancer drugs in HCC treatment. It has toxicity to the hematopoietic function of bone marrow (31,32). Bestatin is a recognized CD13 inhibitor that is constantly used as an adjuvant, which can enhance the immunity and prolong the lifetime of patients with acute adult non-lymphocytic leukemia.…”

Section: Discussionmentioning

confidence: 99%

BC-02 eradicates liver cancer stem cells by upregulating the ROS-dependent DNA damage

Dou

Fang

Zhao

et al. 2017

International Journal of Oncology

View full text Add to dashboard Cite

Cancer stem cells (CSCs) are responsible for chemoresistance, tumor recurrence and metastasis. Reportedly, aminopeptidase N (APN, also known as CD13) is a marker for semi-quiescent CSCs and a therapeutic target in human liver CSCs. In the present study, the effect of BC-02, a compound obtained by conjugating a CD13 inhibitor bestatin and fluorouracil (5-FU), was investigated toward liver CSCs. Tumor spheres formed in serum-free culture conditions have been successfully used to enrich CSCs. In this study, the sphere cells were shown to have several characteristics of CSCs, including drug resistance, high tumorigenicity, epithelial-mesenchymal transition (EMT) phenotype, lower reactive oxygen species (ROS) levels, greater colony-forming efficiency and increased proliferation capacity in vitro. Furthermore, BC-02 effectively suppressed self-renewal and malignant proliferation of CSCs compared with 5-FU, bestatin, and even the combination of 5-FU and bestatin. In addition, cell proliferation was effectively suppressed when exposed to 5-FU plus CD13-neutralizing antibody (CD13 Ab) compared with 5-FU alone. BC-02 can effectively inhibit the activity of CD13. Results demonstrated that CD13 inhibitor BC-02 impaired the properties of liver CSCs by targeting CD13 and upregulating the intracellular ROS and ROS-induced DNA damage. BC-02 might be a potential therapeutic agent for eradicating the liver CSCs and overcoming chemoresistance in liver cancer.

show abstract

“…Because the DO x stays associated with the carrier, it has pharmacokinetics similar to that of the carrier, which results in significantly altered plasma pharmacokinetics for PLD when compared with conventional DO x . This includes significantly higher area under the plasma-concentration-time curve (AUC), increased distribution half-life, lower rate of clearance, smaller volume of distribution, and 15-to 40-fold higher peak concentrations [25][26][27]. Tissue concentrations of DO x are also significantly higher, and remain higher for significantly longer periods of time following delivery via pegylated liposomes, compared with free drug.…”

Section: Liposomalmentioning

confidence: 99%

Reduction of Hepatotoxicity Induced by Doxorubicin

Bengaied¹,

Ribeiro²,

Amri³

et al. 2017

J Integr Oncol

View full text Add to dashboard Cite

Doxorubicin (DOX) has been used in the treatment of variety of cancers but its administration is limited by a dosedependent toxicity. Its cytotoxic effects on malignant cells have shown an increase in the risk of cardiotoxicity, hepatoxicity, renal insufisance.Antioxydants have been explored for both their cancer preventive properties and chemodulatory of DOX toxicity. Resveratrol (RSV) is a polyphenolic constituent of several dietary mainly of grapes and wine origin recently its anticancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. RSV is also known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, RSV possesses great medicinal value, its applications as a therapeutic drug is limited. Problems like low oral bioavailability and poor aqueous solubility make RSV an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of RSV is also a major barrier for its clinical translation. Hence, to overcome these disadvantages RSV-based nanodelivery systems have been considered in recent times. Nanodelivery systems of RSV have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to bring new new insights into the molecular mechanisms of DOX toxicity with respect to DNA damage, free radicals and whether RSV can be a playmaker as chemodulatory of DO x .

show abstract

Activity and safety of pegylated liposomal doxorubicin, 5-fluorouracil and folinic acid in inoperable hepatocellular carcinoma: A phase II study

Cited by 5 publications

References 25 publications

A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma

A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma

BC-02 eradicates liver cancer stem cells by upregulating the ROS-dependent DNA damage

Reduction of Hepatotoxicity Induced by Doxorubicin

Contact Info

Product

Resources

About