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Cutting-edge Treatments for Hepatocellular Carcinoma
The International Liver Cancer Association (ILCA) takes a multidisciplinary approach to furthering the understanding and management of hepatocellular carcinoma (HCC). September 5-7, 2008, researchers from more than 40 countries attended the ILCA’s Second Annual Conference in Chicago, Illinois, to discuss the most recent findings on diagnosis and treatment of HCC.
The ILCA conference features cutting- edge symposia, and this year’s conference included a series of lectures highlighting innovative approaches to treating HCC; as well as general sessions, where the world’s leading clinical experts and researchers discussed recent discoveries about the pathology and molecular pathogenesis of HCC and presented the latest developments in surgical and medical treatments, clinical trials, and targeted therapies. The following summaries offer highlights of key presentations from the ILCA Second Annual Conference.CEUS May Offer Early Evidence of Anti- Angiogenesis
Hui-Chuan Sun and colleagues at the Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China, evaluated whether contrast-enhanced ultrasonography (CEUS) use could identify a correlation between microvessel density (MVD) of HCC and tumor perfusion parameters in human patients. Then, using an animal model, they tested whether CEUS could monitor changes in angiogenesis induced by anti- angiogenesis treatment. The tumor perfusion parameters that CEUS detected include peak intensity, increased peak intensity, increased signal intensity, area under curve, and bloodflow index. These parameters are associated with MVD. In the animal model experiment, researchers administered a vascular EGFR inhibitor to suppress the motility of human umbilical vein endothelial cells; this significantly delayed tumor growth. Investigators noted that changes in tumor perfusion parameters were detectable 3 days earlier than changes in tumor size. This study has important clinical ramifications, indicating that it may be possible to use CEUS to monitor tumor perfusion and identify changes in tumor size, providing earlier biological evidence on the efficacy of anti-angiogenesis treatment. Researchers believe further study is warranted.Researchers Establish Radius of Effect for Doxorubicin-loaded Drug-eluting Beads
Researchers have been conducting clinical investigations on using doxorubicin-loaded drug-eluting beads (DEBs) in the management of HCC prior to liver transplantation. The rationale behind using DEBs to deliver doxorubicin is to decrease systemic concentration of the drug while delivering high doses locally.
A study by Julien Namur, Pharmacy University, Reims, France, and colleagues evaluated explanted livers with HCC from patients who underwent chemoembolization with doxorubicin DEBs prior to transplantation. They sought to determine concentration of doxorubicin in the tissue according to time of explanation.
Doxorubicin was mapped and quantified around 162 different DEBs ranging from 100 to 300 micrometers with a mean dose of 98.3 mg ± 24.4 mg (75- 150 mg). Pathology analysis detected the drug in liver tissue surrounding the DEBs for all times of explantation. Investigators concluded that cytostatic levels of doxorubicin are detectable in a radius of tissue around the DEBs that spans several hundred micrometers. The concentration of doxorubicin in the tissue decreased exponentially in relation to the sample’s distance from the DEB and over time, from day 1 to day 30. This work makes it possible to correlate drug profiles with tissue and cellular damage. It could also facilitate more accurate monitoring of a patient’s therapy progress when DEBs are used.Sorafenib Monotherapy Demonstrates Favorable Efficacy
Joong-Won Park and colleagues at the National Cancer Center, Goyang, South Korea, performed a retrospective study to evaluate the efficacy and safety of sorafenib (Nexavar) in Korean patients with HCC. Many were from areas where chronic infection with hepatitis B virus is endemic. The review included 48 patients with grade 3 or 4 unresectable or metastatic HCC primarily related to hepatitis B (45.8%), hepatitis C (6.3%), or both (2.1%); an ECOG performance status from 0 to 2; and Child-Pugh class A-B. Vascular invasion and extrahepatic spread were observed in 48% and 63% of patients, respectively. All patients had been treated with a starting dose of sorafenib 400 mg twice daily, and tumor response was evaluated by an independent radiologist and a hepatologist.
Two patients (4.2%) achieved a partial response, and 18 (37.5%) achieved stable disease, yielding a disease control rate (DCR) of 41.7%. The DCR was significantly greater in patients without vascular invasion (P = .045). At a median follow-up of 13 weeks, the median time to progression was 7.7 weeks. The most common grade 3 and 4 adverse events included hand-foot skin reaction (8.3%), diarrhea (8.3%), and skin rash (6.3%). Investigators concluded that, for the retrospective series of Korean patients analyzed, monotherapy with sorafenib demonstrated favorable efficacy with modest improvement in survival outcome.
Combined CRT and TACE Provides Local Control for HCC