A Phase II Study of Epirubicin and Thalidomide in Unresectable or Metastatic Hepatocellular Carcinoma

Zhu, Andrew X.; Fuchs, Charles S.; Clark, Jeffrey W.; Muzikansky, Alona; Taylor, Kerry; Sheehan, Susan; Tam, Kayao; Yung, Elizabeth; Kulke, Matthew H.; Ryan, David P.

doi:10.1634/theoncologist.10-6-392

Cited by 40 publications

(27 citation statements)

References 29 publications

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“…Advanced hepatocellular carcinoma (HCC) carries a poor prognosis, and systemic therapy with cytotoxic agents shows no survival benefit (1). The orally available, multitargeting receptor tyrosine kinase inhibitor sorafenib is the first agent showing significant improvement in median overall survival in 2 randomized phase III trials in advanced HCCs (2,3).…”

Section: Introductionmentioning

confidence: 99%

Phase I Dose-Finding Study of Pazopanib in Hepatocellular Carcinoma: Evaluation of Early Efficacy, Pharmacokinetics, and Pharmacodynamics

Yau

Chen

Chan

et al. 2011

Clinical Cancer Research

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Background: A phase I dose-escalating study of pazopanib was conducted to determine the maximum tolerated dose (MTD), pharmacokinetic/pharmacodynamic relationships, and clinical activity in patients with advanced hepatocellular carcinoma (HCC).Experimental Design: Asian patients (N ¼ 28) were dose escalated on pazopanib (200-800 mg) once daily (QD) on 21-day cycles, with MTD as the primary endpoint using a modified 3 þ 3 design. Changes in tumor vasculature were evaluated by dynamic contrast-enhanced MRI (DCE-MRI).Results: Two of five patients at the 800-mg dose level experienced dose-limiting toxicities [grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevations and grade 3 malaise]. The MTD in patients with HCC (Child-Pugh class A) was 600 mg QD. Diarrhea, skin hypopigmentation, and AST elevation were the most commonly reported adverse events at the MTD. Mean C max and area under the concentration-time curve (AUC 0-6 ) of pazopanib and its metabolites did not increase dose proportionally across the 200 to 800 mg range. Reductions in IAUGC and K trans were shown at all pazopanib doses

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Section: Introductionmentioning

confidence: 99%

Phase I Dose-Finding Study of Pazopanib in Hepatocellular Carcinoma: Evaluation of Early Efficacy, Pharmacokinetics, and Pharmacodynamics

Yau

Chen

Chan

et al. 2011

Clinical Cancer Research

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“…Thomas et al [30] showed that in patients with advanced HCC the combination of bevacizumab and erlotinib exerted significant, clinically meaningful anti-tumour activity. Zhu et al [31] documented that sunitinib exhibited modest anti-tumour activity in advanced HCC. We developed GMS, whose size and dissolution time can be manipulated, as an embolic agent [18].…”

Section: Anti-tumour Effects Of Co-treatment Of Tae With Thalidomidementioning

confidence: 99%

Anti-tumour effects of transcatheter arterial embolisation administered in combination with thalidomide in a rabbit VX2 liver tumour model

Nitta-Seko

Nitta²,

Sonoda³

et al. 2011

BJR

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“…It was used in treating advanced HCC patients, mainly due to its anti-angiogenic property. However, single-agent thalidomide [37,38] and its combinations with epirubicin or interferon [39,40] only produced a response rate of 3.1%-6.3% with a median survival of 2.7-6.8 mo. In view of its limited activity and frequent association with treatment-related toxicities, it is now seldom included in the treatment algorithm for advanced HCC patients.…”

Section: Thalidomidementioning

confidence: 99%

Evolution of systemic therapy of advanced hepatocellular carcinoma

Yau¹,

Chan²,

Epstein³

et al. 2008

WJG

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Hepatocellular carcinoma (HCC) commonly occurs in hepatitis B endemic areas, especially in Asian countries. HCC is highly refractory to cytotoxic chemotherapy. This resistance is partly related to its tumor biology, pharmacokinetic properties, and both intrinsic and acquired drug resistance. There is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients. Other systemic approaches, such as hormonal therapy and immunotherapy, have also disappointing results. Recently, encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients. In this review, we concisely summarize the evolution of developments in the systemic therapy of advanced HCC.

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A Phase II Study of Epirubicin and Thalidomide in Unresectable or Metastatic Hepatocellular Carcinoma

Abstract: Background. The median survival time for patients with unresectable hepatocellular carcinoma (HCC) is <6 months, and no effective standard systemic chemotherapy is available. Both epirubicin (Ellence

Cited by 40 publications

References 29 publications

Phase I Dose-Finding Study of Pazopanib in Hepatocellular Carcinoma: Evaluation of Early Efficacy, Pharmacokinetics, and Pharmacodynamics

Phase I Dose-Finding Study of Pazopanib in Hepatocellular Carcinoma: Evaluation of Early Efficacy, Pharmacokinetics, and Pharmacodynamics

Anti-tumour effects of transcatheter arterial embolisation administered in combination with thalidomide in a rabbit VX2 liver tumour model

Evolution of systemic therapy of advanced hepatocellular carcinoma

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