Sunitinib Slows Tumour Growth and Spread of Advanced Liver Cancer: Presented at AACR

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Title: Sunitinib Slows Tumour Growth and Spread of Advanced Liver Cancer: Presented at AACR
URL: http://www.pslgroup.com/dg/21FE3A.htm
Doctor's Guide
April 21, 2008

By Sophie Bainbridge

SAN DIEGO -- April 21, 2008 -- The oral small-molecule tyrosine kinase inhibitor sunitinib may be a therapy option for patients with advanced hepatocellular carcinoma, according to results of a study presented here at the American Association for Cancer Research (AACR) Annual Meeting 2008.

"Patients with advanced liver cancer have a very poor prognosis and the only currently available therapy is sorafenib," explained investigator Andrew X. Zhu, MD, PhD, Director of Liver Cancer Research, Massachusetts General Hospital Cancer Center, and Assistant Professor of Medicine, Harvard Medical School, Boston, Massachusetts.

"This study shows that we may be able to effectively use sunitinib with manageable side effects and give these patients another therapeutic option," Dr. Zhu said at a press briefing on April 14.

Sunitinib is currently approved by the US Food & Drug Administration (FDA) for treatment of metastatic renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumours.

Hepatocellular carcinoma is a highly vascular malignancy associated with a number of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptor 2, and platelet-derived growth factor receptor beta. Sunitinib has activity against these and other receptors, including c-KIT and FLT3. Dr. Zhu and his colleagues reasoned that sunitinib might play a role in the treatment of HCC.

To test their hypothesis, the investigators enrolled 34 patients with unresectable or metastatic HCC and treated them with sunitinib at 37.5 mg/day on a standard regimen (4 weeks on, 2 weeks off). Median age of patients was 63 years (range, 30-81 years) and 85.3% were male.

After 12 weeks of treatment, 1 patient had a partial response and 12 patients achieved stable disease. Median progression-free survival was 4 months (95% confidence interval [CI], 2.8-7.0) and median overall survival was 10 months (95% CI, 7.5-not estimable).

"These results are still preliminary, but they show clear evidence of antitumour activity in these patients," Dr. Zhu said.

The investigators also assessed changes in tumour vascular permeability with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). "We measured these changes because the abnormally increased leakage of plasma from blood vessels in tumours is causally related to pathways blocked by sunitinib," Dr. Zhu explained.

In the analysis of changes in tumour vascular permeability after 2 weeks of sunitinib treatment, the researchers found that mean tumour permeability decreased by an average of 40% from baseline, he reported.

Circulating progenitor cells, a potential marker of cancer spread, were also reduced with sunitinib treatment. "An increase in circulating progenitor cells during therapy appears to be associated with significantly increased mortality in these patients," Dr. Zhu commented. In this study, the number of circulating progenitor cells was significantly decreased by sunitinib at days 15, 29, and 57 compared with baseline (P < .01).

Sunitinib was well tolerated by the patients at the dose used in this study, he said. High levels of aspartate aminotransferase and alanine aminotransferase occurred in 18% and 9% of patients, respectively. Haematological toxicity was also low, and included neutropenia in 12%, lymphopenia in 15%, and thrombocytopenia in 12% of patients. Hyperbilirubinemia occurred in 6% of patients, 9% of patients reported fatigue, and 6% developed hand-foot syndrome.

"Sunitinib can be given safely with close monitoring in the majority of HCC patients. The evidence of antitumour activity with this agent is preliminary, but promising," Dr. Zhu concluded.

Funding for this study was provided by Pfizer, Inc.

[Presentation title: Efficacy, Safety, and Changes in Blood Markers Following Sunitinib Monotherapy in Patients With Advanced Hepatocellular Carcinoma: Experience From a Multidisciplinary Phase II Study. Abstract LB-139]

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