Emerging Approaches in Hepatocellular Carcinoma

Kulik, Laura; Mulcahy, Mary F.; Omary, Reed A.; Salem, Riad

doi:10.1097/mcg.0b013e318060ac52

Cited by 16 publications

(15 citation statements)

References 148 publications

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“…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: 97%

“…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. Patients with metastatic disease are usually treated with palliative care and only have a median survival of a few months [4,22].…”

Section: Discussionmentioning

confidence: 99%

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

Cohn¹,

Myers²,

Mamus³

et al. 2008

Invest New Drugs

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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.

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Section: Discussionmentioning

confidence: 97%

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

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show abstract

“…In addition, the selection of treatment modality for HCC is also highly dependent on the number and size of tumor nodule. For instance, the Milan criteria are widely accepted standards for HCC patients undergoing liver transplantation [8-10], whereas patients undergoing partial hepatectomy usually have a maximal tumor number of two or three. For patients undergoing percutaneous ethanol or acetic acid injection or radiofrequency ablation, the largest size of tumor is usually set at 3 cm and the number of tumor nodule usually does not exceed 3 [11,12].…”

Section: Introductionmentioning

confidence: 99%

Prognostic prediction across a gradient of total tumor volume in patients with hepatocellular carcinoma undergoing locoregional therapy

et al. 2010

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BackgroundThe size and number of tumors are important prognostic indicators for hepatocellular carcinoma (HCC). However, it is difficult to assess the prognosis for patients with a variable number and size of tumors. By combining these two factors, we investigated the role and prognostic accuracy of total tumor volume (TTV) for HCC.MethodsA total of 786 patients undergoing locoregional therapy (transarterial chemoembolization, percutaneous radiofrequency ablation and acetic acid or ethanol injection) for HCC were prospectively evaluated.ResultsThe mean and median TTV was 177 cm3 (range, 0.1-3,591 cm3) and 21 cm3, respectively. Of all, 38%, 29%, 15%, 7% and 11% of patients had TTV of <10 cm3, 10-50 cm3, 50-200 cm3, 200-500 cm3 and >500 cm3, respectively. TTV was significantly larger in patients with higher serum α-fetoprotein (AFP) levels or with vascular invasion. The Child-Turcotte-Pugh score, performance status, vascular invasion, AFP level and TTV were significant independent prognostic predictors in the Cox proportional hazards model. After adjustment, patients with TTV 50-200 cm3 (relative risk [RR]: 1.74, p = 0.009), 200-500 cm3 (RR: 2.15, p = 0.006) and >500 cm3 (RR: 3.92, p < 0.001) had a significantly increased mortality risk in comparison to patients with TTV <10 cm3.ConclusionsTTV is a feasible prognostic predictor across a wide gradient and can be used to predict the mortality risk of HCC. Selecting appropriate cutoffs of TTV may help refine the design of cancer staging system and treatment planning. Future clinical trials of HCC may include this parameter for mortality risk stratification.

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“…1 The incidence of HCC is predicted to continue to increase over the next 30 years. 2 To develop new therapeutic strategies, it is important to elucidate molecular mechanisms underlying hepatocarcinogenesis.…”

mentioning

confidence: 99%

Pigment Epithelium-Derived Factor Inhibits Lysosomal Degradation of Bcl-xL and Apoptosis in HepG2 cells

Kawaguchi

Yamagishi

Itou

et al. 2010

The American Journal of Pathology

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Pigment epithelium-derived factor (PEDF) has several biological actions on tumor cells , but its effects are cell-type dependent. The aim of this study was to examine the pathophysiological role of PEDF in hepatocellular carcinoma (HCC). PEDF expression was examined in various hepatoma cell lines and human HCC tissues , and was seen in various hepatoma cell lines including HepG2 cells. In human HCC tissues, PEDF expression was higher than in adjacent non-HCC tissues. In addition , serum PEDF levels were higher in HCC patients than in non-HCC patients, and curative treatment of HCC caused significant reductions in serum PEDF levels compared with pretreatment levels. In vitro experiments, camptothecin (CPT) was used to induce apoptosis and the effect of PEDF was

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Emerging Approaches in Hepatocellular Carcinoma

Cited by 16 publications

References 148 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

Prognostic prediction across a gradient of total tumor volume in patients with hepatocellular carcinoma undergoing locoregional therapy

Pigment Epithelium-Derived Factor Inhibits Lysosomal Degradation of Bcl-xL and Apoptosis in HepG2 cells

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