A joint team of researchers from Hospital Clinic of Barcelona and Barcelona Clinic Liver Cancer (BCLC) Group has examined 602 advanced liver cancer patients who were divided into two groups: one group was taking Nexavar – sorafenib, the second group was taking a placebo.

Placebo group patients reported an average of 7.9 months of survival rate, while Nexavar group patients reported 10.7 months, which is a 3 month more improvement. This is not a significant improvement, but researchers are excited, because this is the first step toward providing liver cancer treatment. Some patients even had a 3 year long improvement in survival rates.

According to American Cancer Society (ACS) statistics, each year about 21000 Americans are being diagnosed to have liver cancer, an estimated 18,410 people with die from the disease in 2008. Liver cancer mainly occurs among those who were infected with hepatitis B or C virus, this is why they are advised to undergo liver screenings once every 6 months.

Liver cancer treatments are not very effective, especially when the disease is diagnosed late. If it is diagnosed early, it is sometimes possible to remove tumor or to perform transplant surgery. Otherwise, drug treatment methods don’t work, because liver is good in pushing drugs out and detoxifying. Drugs can’t stay long in liver and don’t affect it much.

Nexavar is an approved advanced kidney cancer which is working by reducing the number of cell proliferation and newly growing blood vessels. This means that the drug is not reducing tumor size, it just prevents the tumor from growing.

Researchers are now working on Nexavar, trying to combine it with other drugs and achieve better results. Researchers are also trying to find out how the drug works on different stages of liver cancer. Although the drug is expensive – about $5,000 a month – it is yet the only drug for liver cancer treatment.

By: – Fri, 07/25/2008 – 13:03

Nexavar (sorafenib) is the first and the only approved pill for unresectable or metastatic hepatocellular carcinoma, which are the most common forms of liver cancer treatment. The drug is approved for advanced kidney cancer treatment in 70 countries. It is also approved as liver cancer treatment in 40 countries and now it comes to Chine. Bayer and Onyx plan to apply the drug for approval as breast and lung cancer treatment as well.

Hepatocellular carcinoma accounts for 90% of all liver cancer cases affecting more than 600,000 people annually worldwide. China has the highest number of liver cancer sufferers – 340,000 cases a year. South Korea, Japan and Taiwan together report about 600,000 new cases annually, European counties report 54000 cases, US reports 15000 cases. The number of people affected by liver cancer increase each year, especially in China, this is why Nexavar approval is extremely important for China.

In 2002, liver cancer killed 600,000 people worldwide, out of which 370,000 deaths occurred in China, South Korea and Japan, while European Union saw 57,000 deaths, and United States reported 13,000 deaths.

Bayer and Onyx conducted two Phase 3 clinical trials involving 800 patients, who did not receive any treatment before the study begun. Nexavar was able to effectively target the most important processes in cancer – cell proliferation (growth) and angiogenesis (blood supply).

“This is another significant milestone in a region where patients are in dire need of a therapy that improves survival,” said N. Anthony Coles, MD, president and chief executive officer, Onyx Pharmaceuticals, Inc. “The approval in liver cancer in China comes less than two years after the approval in advanced kidney cancer and proves that Nexavar is and will continue to be an important foundational therapy in multiple patient populations.”

This is how Nexavar treats cancer. Bayer says “Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth.”

By: Ruzanna Haroutiunyan for eMaxHealth – Mon, 07/28/2008 – 12:48

Researchers have previously identified eight genotypes of HBV and a variety of mutations in two regions of the viral genome, referred to as the precore and the basal core promoter. It was not known the extent to which different HBV genotypes or mutations are associated with the risk for liver cancer, which is also called hepatocellular carcinoma.

To find out, Chien-Jen Chen, Sc.D., of the Academia Sinica in Taipei, Taiwan, and colleagues characterized the viral DNA from 2,762 Taiwanese individuals who were infected with the virus but had not been diagnosed with liver cancer at the time of blood collection, which occurred during 1991 and 1992.

After a total follow-up of 33,847 person-years, 153 of these subjects have been diagnosed with liver cancer. HBV genotype C and a particular mutation in the basal core promoter (A1762T/G1764A) were associated with increased risk of liver cancer, while a mutation in the precore region (G1896A) was associated with a decrease in risk.

These data may help identify individuals “who are at an increased risk for liver disease progression and would therefore potentially benefit from early interventions, such as reg¬ular screening to detect disease progression, and treatment,” the authors write.

In an accompanying editorial, Josep Llovet, M.D., of Mount Sinai School of Medicine in New York and Anna Lok, M.D., of the University of Michigan Medical Center in Ann Arbor review the previously known risk factors for liver cancer, prevention strategies to reduce the risk of HBV infection, and treatments for individuals who have already developed liver cancer.

“One of the main challenges is to determine whether secondary prevention can be accomplished with new antiviral therapies for HBV infection,” the editorialists write. When secondary prevention strategies are tested in large randomized trials, patients should be stratified by known risk factors, including viral genotype and mutations.

By: Journal of the National Cancer Institute – Tue, 08/12/2008 – 16:40

For patients with liver cancer (also known as hepatocellular carcinoma), transplantation has been restricted to those who fit the Milan criteria. Their tumors must involve one lesion less than or equal to five centimeters in diameter, or two to three lesions each less than or equal to three centimeters. However, studies have suggested that patients with slightly larger lesions may also do well with a transplant.

Rather than expand the Milan criteria, researchers have suggested down-staging hepatocellular carcinoma to select for tumors with more favorable biology that will respond to treatment and do well following liver transplantation. The impact of successful down-staging on post-transplant outcomes was heretofore unknown.

Researchers, led by Francis Yao of the University of California at San Francisco, conducted a prospective study of down-staging protocol and report intention-to-treat survival, dropout and post-transplant tumor recurrence, along with factors that may influence response to down-staging treatment.

Between June 2002 and January 2007, the researchers enrolled 61 liver cancer patients whose tumor stage exceeded the Milan criteria. Fifty-five of these patients received a combination of laparoscopic radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). The remaining 6 patients underwent resection as the down-staging procedure.

Down-staging was successful in 43 of the 61 patients (70.5 percent), and 35 of those received a liver transplant after a median of 8.2 months. While two of the transplant recipients died (one from graft problems and the other from recurrent hepatitis C infection), the remaining 33 were alive and free of liver cancer recurrence after a median follow-up of 25 months.

In the patients for whom down-staging was unsuccessful, 15 had tumor progression, while 3 died (two related to the down-staging, the other not.)

Comparing the clinical characteristics of the 35 patients who received a liver transplant to the 18 patients with treatment failure, only median alpha fetoprotein (AFP) level was significantly different. Treatment failure was the eventual outcome in seven of the eight patients with pre-treatment AFP > 1000 ng/mL. “High AFP may be a marker for vascular invasion or extra-hepatic disease that escapes detection by conventional imaging techniques,” the authors suggest.

The authors note the heterogeneity of they loco-regional therapy may be a weakness of their study, and that the optimal treatment should be determined on a case-by-case basis. They also point out that 25 months of post-transplant follow-up may be too short to fully determine the risk of liver cancer recurrence.

Still, they conclude, “our results suggest that tumor down-staging to meet conventional criteria for orthotopic liver transplantation (OLT) among carefully selected patients is associated with excellent post-transplant outcome. Down-staging put selection pressure against aggressive tumors that are likely to progress despite treatment, whereas tumors with more favorable histology are more likely to respond to treatment and do well after OLT.”

They call for further studies to refine down-staging treatment strategies to improve the intention-to-treat outcome.

By: Wiley-Blackwell – Fri, 09/05/2008 – 03:57

The scientists tested their new technique on liver tissue samples from 307 patients enrolled in clinical studies in four different countries. The scientists used sophisticated microarray technology to examine RNA from stored liver tissue samples. Their studies turned up a tell-tale genetic profile that indicated whether liver cancer will recur.

Since the testing was done on tissue samples of patients whose clinical outcomes were known, the researchers were able to associate specific “gene expression signatures” with a likelihood of tumor recurrence.

The researchers are optimistic that oncologists will be able to use this information to determine which liver cancer patients would likely develop recurrence and treat them to help prevent it.

“It is now possible to scan the entire genome for gene expression profiles in tissues that have been fixed for a very long time—in our study as long as twenty-four years,” said Howard Hughes Medical Institute investigator Todd R. Golub, who led the study. “There are lots of those tissues available compared with frozen ones, and tissue availability has been a real bottleneck in cancer genomic research.”

The findings were published in an advance online article in the New England Journal of Medicine by an international team including collaborators from Japan, Spain, Norway and Italy.

Liver cancer is the third leading cause of cancer deaths worldwide. Most primary liver cancers begin in liver cells called hepatocytes. This type of cancer is called hepatocellular carcinoma or malignant hepatoma. Although liver cancer is often detected at an early stage, it can recur despite early diagnosis and treatment. If the cancer recurs, it often proves fatal.

For decades, hospitals have stored tissue samples from biopsies and surgeries by soaking them in a combination of formaldehyde and water (called formalin) and then embedding them in wax. However, this type of storage breaks the genetic material into pieces that are so small that they are essentially useless for genetic studies, explained Golub, a researcher at the Dana-Farber Cancer Institute and the Broad Institute of the Massachusetts Institute of Technology and Harvard University.

Golub’s research is based on the premise that extraordinary insights into the molecular basis of cancer can be obtained by taking global views of the genomes of tumor samples. To broaden the view of cancer genomes, Golub and his colleagues use DNA microarrays (DNA chips) to monitor the gene expression (gene activity) of thousands of genes simultaneously across the human genome. This technique, pioneered by HHMI investigator Patrick O. Brown at Stanford University, involves extracting messenger RNA (mRNA) from tumor samples, fluorescently labeling the mRNA and hybridizing it to an array of DNA probes in the DNA chip. By measuring the mRNA levels from each gene, researchers can determine the activity of the genes in the tumor.

“On average, mRNA samples in fresh tissue are around two thousand bases long,” said Golub said. “But when a tissue sample is fixed in formalin, the mRNA gets cleaved into little bits between fifty and one hundred bases long. So, these samples are not amenable to conventional microarray technology.”

However, scientists at Illumina, Inc., in San Diego, had recently developed a way to perform gene expression analysis on these degraded samples. The company had successfully used their technique to study the expression levels of several hundred genes in formalin-fixed samples. “We reasoned that it might work for analyzing the entire genome,” Golub said. Their goal was to measure or infer the activity of roughly 6,000 genes in the samples – a large improvement over the previous method.

To find out if that was feasible, Golub’s team looked at tissue samples from 307 patients enrolled in liver cancer studies in Tokyo, Milan, New York and Barcelona. They first analyzed samples of the tumors themselves, looking for gene expression patterns that might be predictive of cancer recurrence. “You would think that if you wanted to learn about a tumor’s probability of coming back, you would look at the genomic profile of the tumor,” he said. “But we found that the genetic profile of the tumor wasn’t predictive of outcome, survival, or late recurrence.”

However, the paper’s first author, Yujin Hoshida, suggested that they also analyze gene expression in what appeared to be normal liver tissue adjacent to the tumor. Hoshida knew that liver cancer researchers have been debating a hypothesis that a “field defect” of the whole liver may predispose a person to liver cancer. That theory posits that liver tissue that appears normal might in fact harbor detectable genetic abnormalities that would give rise to new tumors after the main tumor was removed. Analysis of this adjacent tissue revealed a characteristic gene expression signature in 186 genes that reliably correlated with a high frequency of tumor recurrence.

“These findings indicate that we might be able to identify patients at risk of recurrence and target those patients with interventions to help prevent it,” he said. “The fact that the predictive information comes not from the tumor but from surrounding tissue could offer important insights into the mechanism of liver cancer.”

More broadly, said Golub, this analytical technique could be applied to any type of cancer. “We don’t know whether there will be a recurrence signature in the non-tumor tissue, of, for example, breast cancer,” he said. “But we can now explore that possibility.” Golub noted that the technique also opens the way for genomic study of fixed tissue samples in diseases, such as multiple sclerosis.

In an accompanying editorial in the NEJM, Morris Sherman of the University of Toronto wrote that the findings “bring the possibility of individualized therapy for hepatocellular carcinoma one step closer.” He wrote that the new research “has opened the door to identifying the relevant gene expression in the pathogenesis of hepatocellular carcinoma as it evolves from non-tumorous liver, as well as possibly initiating research into a molecular method for determining more precisely who is at risk for the development of hepatocellular carcinoma.”

Golub said the next step is to analyze samples from more patients to confirm findings in liver cancer. He said he sees no major barriers to translating the findings into a clinical diagnostic technique, but some technical issues remain to be resolved.

By: Howard Hughes Medical Institute – Mon, 10/27/2008 – 12:17

This molecule is a microRNA, a recently discovered class of tiny molecules used by cells to help control the kinds and amounts of proteins they make. More than 250 different microRNAs have been discovered, and several have been linked to cancer.

These findings show exactly how one specific microRNA, called miR-21, helps cancer develop.

This molecule occurs at unusually high levels in many kinds of cancer cells. The study looked at a gene called PTEN (pronounced P-TEN), which normally protects cells from becoming cancerous. Researchers know that the abnormal silencing of this tumor-suppressor gene contributes to the development of liver cancer and other malignancies.

The findings help explain how liver cancer develops and may identify new drug targets for treating the disease. This particular microRNA might also provide a marker to help determine a patient’s prognosis.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center, is published in the August issue of the journal Gastroenterology. "Our findings essentially describe a new mechanism used by cells to regulate PTEN," says principal investigator Dr. Tushar Patel, professor of internal medicine, director of hepatology and a liver-cancer specialist at Ohio State University Medical Center.

They show that high levels of miR-21 block the PTEN gene, he explained. This, in turn, activates chemical pathways that enable cancer cells to proliferate, migrate and invade other tissues, all of which are features of tumor formation. Patel and his collaborators began the study by measuring the relative levels of 197 microRNAs in normal liver cells and in liver cancer cells from human tumors and in four liver cancer cell lines.

Levels of miR-21 were up to nine times greater in liver-tumor tissue compared with normal liver tissue, twice that of the next highest microRNA.

Earlier research led by Patel had shown that miR-21 probably targeted PTEN, and this study confirmed that.

Furthermore, the researchers showed that adding high levels of miR-21 to normal liver cells caused PTEN levels to drop. They also traced the chemical pathways that increased the cells’ abilities to proliferate, migrate and invade other tissues.

"Our findings indicate that miR-21 plays a fundamental role in tumor-cell behavior and cancer development," Patel says, "and this may also be relevant to other tumors in which miR-21 is overexpressed. If this work is reproduced in investigations of other cancers, it could be a big step forward," he says. Funding from the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and the Scott and White Hospital Foundation supported this research.

By: Ohio State University Medical Center – Tue, 08/07/2007 – 07:36

The Company has used the Special Protocol Assessment (SPA) process to obtain valuable FDA feedback on specific elements of our trial design. By incorporating this feedback into the trial design and with Fast Track designation for the assessment of delaying tumour recurrence following curative resection, Progen is confident that its Phase 3 trial meets the FDA requirements for approval under the Fast Track designation.

Justus Homburg, Progen’s Chief Executive Officer, commented: "We will avail ourselves of the additional FDA access that the Fast Track designation affords us as we proceed towards trial completion. With the FDA feedback we have received to date and Fast Track designation, it is now time to lock trial design and prepare to commence patient recruitment."

The Phase 3 double-blinded placebo-controlled trial is scheduled to be run in countries in North America, Europe and Asia. Approximately 600 patients with post-operative primary liver cancer will be enrolled in the trial. The benefits of this trial design include the treatment of more patients than the Phase 2 program, which strengthens the clinical and statistical significance of the data. Patients will be treated for a longer period of time potentially prolonging the time to recurrence. The double-blinded, placebo-controlled nature of the trial will ensure the best possible data under the most rigorous of conditions.

We remain on track to enroll the first patient into the Phase 3 trial before year’s end. An Asian investigators’ meeting has been held in Thailand, the North American investigators’ meeting is being held this week and one is planned for Europe in the coming weeks. In addition, key sites have submitted the protocol for ethics approval and regulatory submissions have been filed in key countries.

By: Progen Pharmaceuticals Limited – Sat, 11/03/2007 – 09:10

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application for Nexavar (sorafenib) tablets for the treatment of patients with unresectable hepatocellular carcinoma (HCC), or liver cancer. Nexavar, an oral anticancer drug, is the first approved systemic therapy for liver cancer and the only one shown to significantly improve overall survival in patients with the disease. In 2005 Nexavar became the first new treatment in more than a decade for advanced kidney cancer, and is currently approved in more than 60 countries for this indication.

"The approval of Nexavar in liver cancer marks the second time in two years that this novel kinase inhibitor has been granted FDA approval on a Priority Review basis, making it rapidly available to patients who previously had limited treatment options," said Arthur Higgins, chairman of the Executive Committee of Bayer HealthCare. "This milestone will likely establish Nexavar as the standard systemic therapy for the treatment of liver cancer, and is a turning point in improving treatment outcomes in patients facing the devastating impact of this disease."

"Liver cancer is one of the cancers in which the number of related deaths continues to increase," said Hollings C. Renton, chairman, president and chief executive officer of Onyx Pharmaceuticals, Inc. "This second approval for Nexavar demonstrates our commitment to expediting the clinical development of this innovative therapy to treat today’s unmet needs in cancer. We are grateful to the patients, families and investigators who make this important research possible."

HCC, the most common form of liver cancer, is responsible for about 90 percent of the primary malignant liver tumors in adults.(1,2) Liver cancer is the sixth most common cancer in the world and the third leading cause of cancer-related deaths globally.(3) More than 600,000 cases of liver cancer are diagnosed worldwide each year(3) (about 19,000 in the United States,(4) 54,000(5) in Europe,(6) and 390,000 in China, Korea and Japan(6)) and incidence is increasing.(7) In 2002 approximately 600,000 people died of liver cancer including 13,000 in the United States, 57,000(5) in Europe and approximately 360,000 in China, Korea and Japan.(6) Currently, the 5-year survival rate for liver cancer patients in the United States is 11 percent.(8)

"The American Liver Foundation (ALF) is always pleased when new therapies prove effective for those affected by liver disease. Researchers worldwide, including those supported by ALF, have spent decades studying liver cancer," said James L. Boyer, M.D., chairman, board of directors, American Liver Foundation. "This new treatment provides a valuable option for liver cancer patients and will enable ALF to further promote the treatment of liver disease through our education and advocacy efforts."

The companies also announced that an innovative patient support program – Resources for Expert Assistance and Care Helpline (REACH(R)) – is available to answer questions about Nexavar treatment, reimbursement, and patient support. For more information, healthcare providers and patients may contact the REACH program at 1.866.NEXAVAR (1.866.639.2827).

Nexavar Phase 3 Data Summary

The FDA approval was based on positive data from the international Phase 3 placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial which demonstrated that Nexavar improved overall survival by 44 percent in patients with HCC (HR=0.69; p=0.0006) versus placebo. In the study, median overall survival was 10.7 months in Nexavar-treated patients compared to 7.9 months in those taking placebo. No indication of imbalances was observed in serious adverse events between the Nexavar and placebo-treated groups with the most commonly observed adverse events in patients receiving Nexavar being diarrhea and hand-foot skin reaction. Based on these data, the European Commission granted marketing authorization to Nexavar for the treatment of patients with hepatocellular carcinoma on October 29, 2007.

Nexavar’s Differentiated Mechanism

Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. Preclinical models have also demonstrated that Raf/MEK/ERK has a role in HCC; therefore, blocking signaling through Raf-1 may offer therapeutic benefits in HCC.

Important Safety Considerations for U.S. Patients Taking Nexavar

Based on the currently approved package insert for the treatment of patients with unresectable hepatocellular carcinoma, hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed. Bleeding with a fatal outcome from any site was reported in 2.4% for Nexavar vs. 4% in placebo. The incidence of treatment-emergent cardiac ischemia/infarction was 2.7% for Nexavar vs. 1.3% for placebo. Most common adverse events reported with Nexavar in patients with unresectable HCC were diarrhea, fatigue, weight loss, anorexia, nausea and hand-foot skin reaction. Grade 3/4 adverse events were 45% for Nexavar vs. 32% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast- feeding. In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.

For information about Nexavar including U.S. Nexavar prescribing information, visit www.nexavar.com or call 1.866.NEXAVAR (1.866.639.2827).

By: Bayer HealthCare Pharmaceuticals – Mon, 11/19/2007 – 17:41

“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. “Giving these patients more options would have a significant impact.”

Hepatocellular carcinoma is a cancer that relies heavily on blood vessels for growth; sunitinib controls the growth of blood vessels and could therefore potentially play an important role for treatment, Zhu says.

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 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,” Zhu said.

Researchers also measured changes in tumor vascular permeability using 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 percent 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, Zhu says, noting that an increase in circulating progenitor cells during treatment appears to be associated with significantly increased mortality.

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

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

By: EurekAlert – Wed, 04/23/2008 – 14:53

%26quot;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,%26quot; said Andrew X. Zhu, M.D., Ph.D., director of liver cancer research at Massachusetts General Hospital Cancer Center. %26quot;Giving these patients more options would have a significant impact.%26quot;

Hepatocellular carcinoma is a cancer that relies heavily on blood vessels for growth; sunitinib controls the growth of blood vessels and could therefore potentially play an important role for treatment, Zhu says.

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 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," Zhu said.

Researchers also measured changes in tumor vascular permeability using 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 percent 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, Zhu says, noting that an increase in circulating progenitor cells during treatment appears to be associated with significantly increased mortality.

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

By: EurekAlert – Fri, 04/25/2008 – 14:36