New Drug May Slow Growth and Spread of Liver Cancer

Treatment with a new drug called sunitinib has been shown to slow tumor growth and reduces the risk of metastasis in patients with hepatocellular carcinoma, an aggressive cancer of the liver.

"Patients with this type of liver cancer have a very poor prognosis and the only currently available therapy is sorafenib. This study shows that we may be able to effectively use sunitinib with manageable side effects,” said Andrew X. Zhu, M.D., Ph.D., director of liver cancer research at Massachusetts General Hospital Cancer Center (Boston, MA, USA). "Giving these patients more options would have a significant impact.”

Hepatocellular carcinoma is a cancer that relies greatly on blood vessels for growth; sunitinib controls the growth of blood vessels and therefore can potentially play an important role for treatment, according to Dr. Zhu.

Researchers enrolled 34 patients with advanced liver cancer and gave them 37.5 mg sunitinib daily on a standard four weeks on, two weeks off regimen. Sunitinib is a small-molecule tyrosine kinase inhibitor that targets multiple receptors, including vascular endothelial growth factor receptor 2 (VEGFR2), c-Kit, and FLT3. These receptors may be present in cancer cells as well as in endothelial and immune cells.

By 12 weeks, one patient had a partial response and 17 patients had stable disease. The median progression-free survival was four months and the median overall survival was 10 months. "Results are still preliminary, but there is clear evidence of an anti-tumor activity in these patients,” Dr. Zhu said.

Researchers also measured changes in tumor vascular permeability using magnetic resonance imaging (MRI), because the abnormally increased leakage of plasma from blood vessels in tumors is causally related to pathways blocked by sunitinib. They found that permeability decreased after treatment with sunitinib by 40% compared to measures taken at the start of the study.

Circulating progenitor cells, a potential measure of the risk of cancer spread, also were reduced with sunitinib treatment, according to Dr. Zhu, noting that an increase in circulating progenitor cells during treatment appears to be associated with significantly increased mortality.

Researchers reported that the patients tolerated the sunitinib treatment. High levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) liver enzymes were noted in 18% and 9% of patients, respectively. Blood disorders such as neutropenia (12% of patients), lymphopenia (15%), thrombocytopenia (12%), and hyperbilirubinemia (6%) also occurred at low rates. Fatigue was observed in 9% of patients and hand-foot syndrome in 6% of patients.

The findings of the study were presented in April 2008 in San Diego, CA, USA, at the annual meeting of the American Association for Cancer Research.


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Massachusetts General Hospital Cancer Center