Liver Cancer News 2011
Bristol-Myers: Experimental Liver Cancer Drug failed in Late-Stage Study; Other Tests Continue
22 Dec 2011
The New York based company announced that brivanib, given to patients who had not succeeded with the cancer drug sorafenib, did not increase overall survival. Brivanib, a pill that blocks receptors involved in the growth of cancerous cells, has been tested on more than 4000 patients in 29 studies around the world. An analysis of secondary goals will be presented at an upcoming scientific meeting. Dr. Brian Daniels, senior vice president for global development and medical affairs for Bristol-Myers, said:” We remain committed to the development of brivanib as a potential treatment option for patients with liver cancer.” Results of an ongoing study of the drug are expected next year.
Jennerex Announces First Patient Treated in Phase 2a Clinical Trial of JX-594 as a Neoadjuvant Therapy in Colorectal Cancer Patients Undergoing Surgery
21 Dec 2011
The trial is being conducted to see if the drug can help in patients who are undergoing surgery to treat colorectal cancer that has spread to the liver. Study leader, Rebecca Auer, M.D., surgical oncologist at the Ottawa Hospital, Ottawa, Canada, says approximately 20 patients with colorectal cancer metastases to the liver will receive a single dose of JX-594 two weeks before surgical resection. Patients will be evaluated for evidence of pathologic response, progression-free survival and overall survival. “…This study will allow us to expand our analysis of the multi-mechanistic therapeutic activity of JX-594…” according to John C. Bell, PhD. senior scientist, cancer therapeutics Ottawa Research Hospital.
Chinese Doctors Find Way to Detect Liver Cancer Earlier
19 Dec 2011
Doctors at Zhongshan Hospital, a medical institution affiliated with Fudan University, developed a simple blood test that they say can raise the accuracy of tests for early-stage liver cancer to almost 90 percent. Dr. Fan Jia, vice president of the hospital, said that doctors have found that seven microRNAs, or ribonucleic acid molecules, have a strong connection to liver problems. Fan said just one milliliter of a patient’s blood can show whether the patient had liver cancer, even small tumors less than two centimeters in diameter. The test will cost only about 15.9 U.S. dollars. Results have been published on the website of the Journal of Clinical Oncology.
Celsion Completes Consultative Review Process Wit EMA for Phase III HEAT Study of ThermoDox(R) in Primary Liver Cancer
19 Dec 2011
Celsion announced that it has received written, scientific advice from the European Medicines Agency (EMA) that confirms the efficacy of the HEAT study. The next step is submission of a marketing authorization application (MAA). The EMA also gave the company the green light to establish multiple manufacturing sites of ThermoDox (R) outside the United States to better market the drug. This outcome means Celsion can proceed with a centralized filing in Europe, which will clear a regulatory pathway for approval outside the United States. This sanction would make it easier for other governments around the world to approve the drug in their respective countries.
Transgene Teams with French Cancer League to Discover Cancer Targets
16 Dec 2011
French immunotherapeutics firm Transgene and Ligue National Contre le Cancer are partnering to fight primary liver cancer. Transgene licensed rights to develop the engineered oncolytic JX584 from Jennerex in September 2010. The two French firms started a phase IIb clinical trial, Traverse, last month for treatment of patients who have failed prior therapy with Nexavar (sorafenib). Advanced liver cancer patients who received a highs dose of JX594 have a survival rate twice that of those that received a low dose.
Novel Therapeutic Approach to Combat Liver Cancer Identified
10 Dec 2011
Scientists at Dana-Farber Cancer Institute in the U.S. have identified a mechanism that triggers inflammation in the liver and transforms normal cells into cancerous ones. Among a recently discovered class of micro regulators in mice, the scientists found that a particular micro-RNA, (called miR-124), could be harnessed to treat or even prevent liver cancer. Dimitrios Iliopoulos, of Dana-Farber’s Department of cancer Immunology, and his colleagues found that miR-124 and another micro-RNA interrupted the mechanism that sets up an inflammatory state in the cells that leads to liver cancer. Iliopoulos hypothesized that boosting activity of miR-124 might spike activity in the other micro-RNA which would halt tumor growth.
Radiofrequency Electromagnetic Fields Could Block Spread of Cancer Cells
7 Dec 2011
University of Alabama Birmingham researchers used an intra buccal spoon-shaped probe to deliver amplitude-modulated electromagnetic fields to HCC cells in vitro to replicate in vivo conditions. The cancer cells were exposed to tumor-specific modulation frequencies, which were previously determined using biofeedback methods in cancer patients. HCC cell proliferation began to decrease after 7 days with a greater increase over a 7-week period. Regular hepatocytes and breast cancer cells showed no anti-proliferative effect from HCC-specific frequencies or randomly chosen modulation frequencies. Researchers concluded that the cancer fighting effect of modulation frequencies is both tumor and tissue specific.
4SC Receives Key Patent for Oncology Compound Resminostat in Japan
7 Dec 2011
4SC granted an exclusive license to Yakult Honsha in April to develop and market the drug in Japan. This patent covers the composition of resminostat in the country to fight cancer, as well as other therapeutic uses.
Provectus Reports on Third End-of-Phase 2 Meeting with U.S. FDA to Define Pathway to Approval of PV-10 for Metastatic Melanoma
29 Nov 2011
Provectus Pharmaceuticals, Inc. is a development-stage oncology and dermatology biopharmaceutical company based in Knoxville, Tennessee. PV-10 is an oncology drug designed to selectively target and destroy cancer cells without harming surrounding tissues, Due to an extensive reorganization within the FDA, Provectus has launched the new Division of Oncology Products 2 (DOP 2) to take over review responsibility of PV-10.
Craig Dees, Ph.D, CEO of Provectus has confirmed that this reorganization: “… should benefit us as we prepare to commence Phase 2 testing of PV-10 for HCC.”
Celsion Receives DMC Recommendation to Continue with Phase III Liver Cancer Trial
28 Nov 2011
The independent data monitoring committee (DMC) gave the go-ahead concerning Thermodox, a drug intended to fight primary liver cancer in combination with radiofrequency ablation treatment (RFA). Out of 613 patients in the trial, 219 achieved progression-free survival (PFS). Celsion needs 380 PFS to reach the planned final analysis of the study and company CEO, Michael H. Tardugno says, “Critically, we have the potential to realize a successful outcome to the study prior to its planned completion.”
Liver Cancer Treatment Turns Up the Heat on Chemotherapy
21 Nov 2011
Doctors at Froedtert Hospital in Milwaukee, Wisconsin, have resurrected a little known procedure, called perfusion, to fight liver cancer. In the process, a long incision is made in the abdomen of the patient and the liver is isolated from the rest of the body with clips, catheters and cannulas. The cancer fighting drug malphalan is mixed at a concentration 20 times stronger than standard chemo doses and heated to about 102 degrees. The liver is then bathed in the drug and cancer cells start to die within an hour and continue to do so for days. The procedure itself lasts about an hour and, according to T. Clark Gamblin, M.D. at Froedtert, “The trick is to get the right mix of chemo, heat and time…’ for maximum effect. Some healthy cell death occurs, but is considered an acceptable risk in light of the liver’s regenerative powers. David Bartlett, M.D. cancer surgeon at the University of Pittsburgh Medical Center says 25 perfusions are performed annually at the institution with an average survival rate of two years.
Celsion Reports Third Quarter 2011 Financial Results and Provides Business Updates
10 Nov 2011
The HEAT Study, where Celsion’s proprietary heat-activated liposomal encapsualtion of doxorubicin is in Phase III, has reached its target enrollment of 600 patients. The study is being conducted under a U.S. FDA Special Protocol Assessment, has received Fast Track Designation and has been designated a Priority Trial for liver cancer by the National Institutes for Health. According to Michael H. Tardugno, Celsion’s President and CEO, “The Company remains well funded to execute this study to final data readout, which we continue to anticipate in late 2012.
Jennerex Presents Final Data from JX-594 Randomized Phase 2 Clinical Trial Showing Statistically Significant Survival Benefit in Patients with Advanced Liver Cancer
5 Nov 2011
A private, clinical-stage biotherapeutics company, Jennerex, Inc. presented its findings at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases in San Francisco. JX-594 is an engineered oncolytic virus designed to attack cancer cells in three ways: 1) viral replication, 2) shutdown of tumor blood supply through vascular destruction and 3) active immunotherapy. Median overall survival for high and low dose groups was 13.8 months versus 6.7 months. Percent of patients alive at one year was 66% versus 23% in high and low dose groups, respectively. In addition, JX-584 showed mild side effects with patients experiencing flu-like symptoms that passed within 24 hours. The data were presented by Tony Reid, M.D., Ph.D, professor of medicine, hematology/oncology at Moores Cancer Center at UC San Diego.
Seeking Solutions for Liver Cancer with Cirrhosis
4 Nov 2011
From LiverSupport.com, Nicole Cutler, L.Ac. reports of a small Japanese study published in an August 2001 edition of the New England Journal of Medicine. Takahiro Yamasaki and colleagues from Yamaguchi University Graduate School of Medicine in Ube, Japan have tested the efficacy of the drug Deferoxamine in patients with primary liver cancer and cirrhosis. The drug has an anti-proliferative effect on tumor cells, is an iron chelator, induces apoptosis and has inhibited precancerous growth in animal subjects. In the study, 90% of participants had hepatitis B or C infection and 70% had either Child-Pugh grades of B or C. The overall response rate to Deferoxamine was 20% which researchers believe warrants testing in patients with Child-Pugh class B or C hepatitis and liver cancer.
Jennerex Announces First Patient Randomized in Phase 2b Clinical Trial of JX-594 in Liver Cancer
4 Nov 2011
Jennerex, together with international partners, has launched TRAVERSE, a trial evaluating the use of JX-594 in liver cancer patients who have failed prior therapy with sorafenib. According to David H. Kim, M.D. president and chief medical officer of Jennerex: “JX-594, with its targeted, multi-mechanistic approach, could offer liver cancer patients a distinct therapeutic alternative, even after they have failed all approved treatment options.” TRAVERSE will enroll 120 patients with advanced liver cancer who have failed sorafenib therapy at 45 sites in North America, South Korea, Taiwan, Hong Kong and Europe with the primary objective of determining overall survival benefit for patients receiving the drug.
North Penn Junior Places First in Drexel College of Medicine Competition
2 Nov 2011
Lijia Xie, 16, a junior at North Penn High School in Towamencin Township, Pennsylvania has conducted research into an improved method of detecting liver cancer. Under the mentorship of Drexel and the National Cheng-Kung University Medical Center of Taiwan, Xie used tissue samples from cancer patients as possible biomarkers that can look for the presence of cancer in other patients. The current method of detecting liver cancer misses about 50% of cases. The research, “Specificity of the Methylated RASSFIA Gene as a Biomarker for the Detection of Hepatocellular Carcinoma” could “… pick up 90% of people that are missed by current liver cancer tests,” Xie said. The findings are preliminary, but Xie hopes it will lead to actual methods of clinical testing.
Delcath’s ChemoSat Goes Another Round with the FDA
28 October 2011
ChemoSat is an organ-targeting chemotherapy system that isolates the agents to the desired organ. The FDA refused Delcath’s new drug application (NDA) earlier this claiming the company provided insufficient information for review. The company has a new pre-NDA meeting with the FDA in mid-January 2012. Delcath won CE Mark approval in the European Union in April where the device is considered a Class III medical device. For the company, “This translates into about 95% of the world market outside the U.S.,” according to CEO Eamonn Hobbs. “If I had to choose between the two regulatory approvals, I would take the one we got, the CE Mark, far ahead of the FDA’s, from a commercial perspective.”
New Procedure For Liver Cancer Treatment
25 October 2011
A year after Cheryl Colehour had survived breast cancer, instead of being cancer-free doctors told her there was a tumor on her liver. James Park, MD, University of Washington Medical Center, said the tumor was small and hadn’t spread so surgery was an option. The liver resection was much less invasive because of a smaller-than-normal incision to the patient made with a device call the Davinci Robot. Dr. Park is the first to use the device in the Pacific Northwest. A smaller incision means a quicker recovery and Mrs. Colehour was able to start her chemotherapy much quicker. She is only the third patient to undergo the procedure at UW and one of only a handful nationwide.
US Biomedical Company Signs MOU with Taiwan
22 October 2011
Polaris Group, a California-based biomedical company, signed a memorandum of understanding (MOU) with the Hsinchu County Government in a bid to develop a targeted therapy for liver cancer in Taiwan. The MOU stipulates that Polaris is expected to invest $49.5 million (US) to build a research and development center in Hsinchu Biomedical Science Park, to be completed in three years. The drug to be used, ADI-PEG 20 is an arginine-depleting drug that has demonstrated anti-tumor activity in more than 10 other types of cancer. ADI-PEG 20 entered phase III clinical trials in the U.S. in July this year to treat patients with liver cancer. Polaris decided to collaborate with the Hsinchu County because 90% of its capital comes from the Taiwanese government, which is very keen to develop a drug that would combat liver cancer, the nation’s second highest cancer killer.
Progen Pharmaceuticals Receives Second IND Application Approval in Asia for Liver Cancer Drug
17 October 2011
Medigen Biotechnology Corporation, a licensee of Progen, has been authorized to open sites and begin patient enrollment under its PATRON Phase III study of the liver cancer drug, PI-88. The drug was recently approved in Taiwan, as well. The randomized, placebo-controlled, multinational trial will enroll 500 patients, mostly in Asia, to confirm efficacy and safety of PI-88 in the adjuvant treatment of liver cancer after surgical resection. The goal is disease-free survival in patients.
AFP Level Predicts Mortality in Hepatitis C-Related Liver Cancer
12 October 2011
In patients with hepatitis C-related liver cancer the serum-alpha-fetoprotein (AFP) level around the time of the liver cancer diagnosis is an independent predictor of mortality, according to Dr. Gia L. Tyson of the Houston VA Health Services Research and Development Center of Excellence and Baylor College of Medicine. AFP level has been incorporated into at least three major diagnostic scoring systems for liver cancer outside the U.S., but this study proves that it can be a predictor in U.S. patients, as well. Such testing is inexpensive, widely available and easily interpretable, says Dr. Tyson. While this is the largest study of its kind in the U.S., Dr. Tyson says it was limited in that most of the patients were white men so that the findings may not be generalizable to other racial/ethnic groups.
Onyx Shares up on New Agreement with Bayer on Cancer Drug—Update
12 October 2011
Onyx Pharmaceuticals, Inc. and Bayer Healthcare have restructured their partnership for the global development and marketing of the liver cancer drug, Nexavar. Currently approved in 100 countries, Nexavar is used in the U.S. for the treatment of unresectable liver cancer and advanced kidney cancer.
Scripps Florida Scientist to Study Hepatitis C
10 October 2011
The National Institutes of Health has awarded the Scripps Research Institute a $2.2 million grant to study how the hepatitis C (HCV) virus induces liver cancer with the goal of finding new therapies for treating those chronically infected with the virus. Timothy Tellinghuisen, assistant professor on the Florida campus of Scripps, is the principal investigator on the project. How HCV induces liver cancer is unknown, but Tellinghuisen’s research points to a host protein, CARD 14, that enables replication of the virus in the body without detection by the body’s immune system. The grant will enable Tellinghuisen and his team to identify how the virus manipulates this protein and every step of the cell creation process as well as the function of CARD 14in normal liver physiology.
Saffron Take On Cancer
8 October 2011
In a report in the September issue of Hepatology researchers have found the spice to inhibit the actions of key proteins that contribute to human liver cancer cell proliferation and inflammation. In addition, other evidence shows that saffron switches on programmed cell death in cancerous cells. Researcher on the study Amr Amin, molecular biologist at United Arab Emirates University in Al-Ain said: “The exact mechanism of the anticancer effect of saffron is unclear.” Tapas Saha, a molecular biologist at the Georgetown University Lombardi Cancer Center who didn’t work on the study said that it was “… good work…” but said scaling up these findings to a treatment would be difficult. Saffron is handpicked and expensive but synthetic versions might be more workable.
Study Finds Liver Cancer Increasing in Low Risk Countries, Decreasing in High Risk Countries
6 October 2011
The study, to be published in an upcoming issue of Cancer Epidemiology Biomarkers and Prevention, found the incidence of liver cancer in men and women from 1993 – 2002 went up in economically developed countries in Western Europe, North American and Oceania. The study speculated that chronic HCV infection caused by unscreened blood transfusions for medical purposes and contaminated needles from intravenous drug users may be to blame for the spike. Meanwhile, liver cancer rates for men and women decreased in Asia. Despite the disparity, incidence rates overall in Asian countries are three to four times higher than those in low-risk area with increasing rates. Melissa M. Center, MPH, and one of the authors of the study hopes that:” …Our description of international liver cancer incidence trends may stimulate studies to further illustrate etiologic factors associated with these divergent liver cancer trends worldwide.”
Obesity May Explain Liver Cancer Hike Among Latinos
3 October 2011
Although liver cancer is most common in Asia and Africa, the disease is on the rise in the U.S., primarily due to hepatitis C, according to the New England Journal of Medicine. In 1980, liver cancer incidence was 1.7 cases per 100,000, but by 2005 this had increased to 5 per 100,000, noted lead author of a Texas study, Amelie Ramirez, Dr. P.H, Director of the Institute for Health Promotion at the University of Texas Health Science at San Antonio. Ramirez and her colleagues found that Latinos accounted for one third of liver cancer cases in Texas and about 75% of cases in South Texas from 1995 – 2006. The rates were 10.6 cases per 100,000 in Texas and 9.7 per 100,000 in South Texas, compared to 7.5 per 100,000 among Latinos nationally. Across all three populations, 70% of the cases were men. During the same time period, researchers found among Texas Latinos, the obesity rate was 30% and 35% among South Texas Latinos compared to 27% for Latinos nationally. The fastest growing U.S. minority, Latinos comprise 20% of total population and 36% of population in Texas. By 2030 they will be the majority in the state. Ramirez used data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program, the Texas Cancer Registry, and the Texas Department of State Health Services.
High Risk of Salvage Transplant Failure Post Liver Resection
30 September 2011
According to a study published online in the Sept. 19 issue of Hepatology, initial liver resection in liver cancer patients with Milan criteria is a valid treatment for those with good liver function who develop recurrence within Milan criteria. However, transplantation has a high rate of failure for those with recurrence beyond Milan criteria, said David Fuks, M.D. from the Beaujon Hospital in Paris. Fuks concludes that salvage transplantation under these conditions advocates the use of tissue analysis as selection criteria for only select patients with favorable oncological factors.
Liver Cancer Drug Provectus Receives Orphan Drug Designation From FDA
29 September 2011
The U.S. FDA has made the award to Provectus for Rose Bengal, the active component in their new oncology medication PV-10. In this injectable formulation, Rose Bengal is designed to target liver cancer and the Phase I study results are promising. Provectus is designing a Phase II trial. The compound has been used for over 30 years by ophthalmologists to evaluate eye damage and is deemed safe due to its short half-life and excretion through the body.
AngioDynamics Completes Enrollment in European NanoKnife (R) System Trial for Primary Liver Cancer
29 September 2011
AngioDynamics, a provider of minimally invasive medical devices for vascular access, surgery and peripheral vascular diseases has sponsored this trial to evaluate the safety and efficacy of the NanoKnife(R) System for early-stage liver cancer (tumors 1-3 cm.) Because patients will have not had other treatments any tumor response will be directly attributable to the NanoKnife System, according to President and CEO Joseph DeVivo. Study subjects will be allowed one retreatment. The study is titled:” A Prospective, Multi-Center, Clinical Trial Using Irreversible Electroporation (IRE) for the Treatment of HCC.” It is being conducted on 26 subjects at five European sites by Jordi Bruix of the Barcelona Clinic Liver Cancer (BCLC) Group of the University of Barcelona and Professor Riccardo Lencioni of the University of Pisa School of Medicine. During the study there have been no 30-day mortalities and no serious adverse events.
An Antibiotic Found in Liver of Sharks Could Revolutionize Human Medicine
20 September 2011
Dr. Michael Zasloff, from Georgetown University, led a study that discovered that squalamine, a natural antibiotic found in sharks’ livers, “…produced antiviral activity against the human pathogens found in the diseases such as forms of hepatitis which cannot currently be treated.” Zasloff was interested in sharks because of their primitive, but very effective immune system and discovered squalamine in 1993. Since 1995, he has found a way to synthesize the drug in the lab. He found that the compound inhibited the growth of rapidly growing blood vessels, such as those found in tumors and certain retinal diseases. Squalamine disrupts proteins used to replicate viruses, which indicates that the compound might be designed to fight certain viral infections. “In tissue culture studies squalamine was shown to inhibit the infections of human blood vessel cells by the dengue virus and human liver cells infected with hepatitis B and D…”said Zasloff.
Soy peptide + Chemo Drug Block Colon Cancer’s Spread to Liver
19 September 2011
University of Illinois researcher Elvira de Mejia authored a study in the most recent issue of Cancer Letters that has found that the soy peptide lunasin binds to a receptor in highly metastatic colon cancer cells in mice, preventing them from attaching to the liver. When used with the chemotherapy drug oxaliplatin, Mejia “…saw a six-fold reduction in the number of new tumor sites.” Most colon cancer deaths are caused when the cancer spreads to the liver and, because the process of metastasis is not well understood, chemotherapy has targeted the primary tumor. This study shows that lunasin can not only penetrate the cancer cell and kill it, but also interact with at least one receptor in a cell ready to metastasize preventing it from forming new blood vessels and differentiating. The reduction in metastasis was achieved using 25 daily grams of soy protein, the FDA recommended amount. The next step will be to incorporate lunasin into the animals’ diet, rather than injecting, to see if digestion and absorption alter the efficacy of the treatment.
7 Possible Biotech Takeover Targets
18 September 2011
Exelixis is a small biotech company seeking FDA approval for Cabozantinib. The drug is in Phase II clinical trial for the treatment of liver cancer, as well as a number of other cancers.
‘Micro’-chemo and Cancer Pill Combo Tested in Liver Cancer Patients
9 September 2011
The Journal of Clinical Oncology reports that Johns Hopkins investigators used a combination of sorafenib, orally, and doxorubicin via chemoembolization to achieve better results than the two drugs independently. Jean-Francois Geschwind, M.D. professor of radiology, surgery and oncology at Hopkins reported that for the 35 participants with inoperable liver cancer the procedure added 10-15 months of survival. The patients had no more side effects than reported for either drug alone. A Phase III trial is under way at Johns Hopkins and 100 other sites in the U.S. comparing chemoembolization with or without sorafenib. Says Geschwind:” We’re on the path to improving the standard of care for liver cancer.”
NIH Awards $500K in Grants to Projects Studying miRNAs as Biomarkers
8 September 2011
Hushan Yang of Thomas Jefferson University was awarded the grant to investigate how microRNAs influence how hepatitis B can lead to liver cancer. Yang says HBV is:’ …the most prominent etiologic factor,” for liver cancer, but only 20% with the virus develop the cancer. Their goal is to identify microRNA biomarkers in patients with HBV infection that can predict who will get the disease. Their two-stage study will examine a “highly homogenous Asian-American population,’ as well as a larger, more ethnically diverse group which greatly increases their chances of finding the biomarkers. The investigators also hope to develop a risk-assessment model to analyze cumulative and interaction effects between the biomarkers that can transform chronic HBV infection into liver cancer.
Jennerex Presents Interim Clinical Data of JX-594
6 September 2011
Jennerex, the private clinical-stage biotherapeutics company, presented at the Fifth International Liver Cancer Association (ILCA) in Hong Kong. The Phase II trial enrolled a total of 15 patients, including a subgroup of 10 who have failed previous treatments with sorafenib. All patients had advanced liver cancer. The group was administered a combination of intravenous and intratumoral injections of JX-594 prior to standard sorafenib therapy. Tumor response was observed in 8 of 11 patients for up to 15 months post treatment. Significant tumor reduction following treatment occurred in 6 of 7 sorafenib resistant patients.
BioAlliance Pharma: Presentation of Livatag(R) Survival Results at the International Liver Cancer Congress in Hong Kong
5 September 2011
BioAlliance announces Phase II clinical trial results of its orphan product, Livatag(R), at the International Liver Cancer Association. Pr. Philippe Merle, Professor of Hepatology at the Hospices Civils de Lyon and principal investigator of the trial presented preliminary survival results in patients with unresectable liver cancer. Survival for patients treated with the drug versus the control group was 31.7 months median versus 15 months. Patients who received 3 injections had increased median survival: 33 versus 15 months. The trial had been put on hold due to severe pulmonary adverse events, but Pr. Merle stated that a new, slow intravenous administration route would control this problem.
Radioembolization Attains Survival in Liver Cancer
29 August 2011
A study involving 325 liver cancer patients across eight facilities in Europe indicates that this liver-directed therapy can achieve survival in patients. Most patients (83.6%) were classified as having intermediate to advanced-stage cancer. Between September 2003 and December 2009 most patients received one administration, 6% two and 0.9% three treatments with an overall median survival rate of 12.8 months. Those with less progressed disease and liver involvement survived a median of 24.4 months.
Hawaii Received Funding for Liver Cancer Research
24 Aug 2011
The National Cancer Institute has awarded a five-year, $2.3 million grant to Gordon Okimoto, Ph.D., a research scientist at the UH Cancer Center and Sandy Kwee, M.D. director of positron emission tomography (PET) research at the Queen’s Medical Center. The researchers will use PET to measure specific molecules in the body that have the potential to detect liver cancer, as well as profile global gene expression in cancer-prone and normal tissue samples. From this they will compile a catalog of novel cancer-related molecules that will aid in early detection of the disease. The incidence of liver cancer in the U.S. is rising and Hawaii has the highest death rate in the country.
Delcath Announces Encouraging Top-Line Results From Hepatobiliary Cohort in Phase II Trial of Chemosaturation System
22 Aug 2011
Delcath, a developmental stage specialty pharmaceutical and medical device company, has a proprietary system for chemosaturation, which is designed to administer high dose chemotherapy and other therapeutic agents to diseased organs or regions of the body, while controlling the systemic exposure of those agents. Using the drug melphalan in the Phase II trial, Delcath reported confirmed partial response or durable stable results for its five liver cancer patients with unresectable liver tumors. “We believe these results show a strong signal of efficacy and support our plan to initiate Phase III and Phase IV trials for liver cancer in the second half of 2012,” said Eamonn P. Hobbs, President and CEO of Delcath System, Inc.
Five Strategies Suggested to Reduce Liver Cancer Recurrence
22 Aug 2011
Christian Toso, M.D., Ph.D., and colleagues from Geneva University Hospitals in Switzerland have developed potential strategies to decrease the rate of liver cancer recurrence in liver transplant patients. They include select patients with low baseline levels of circulating liver cancer cells before transplantation; decrease peri-operative release of liver cancer cells by careful handling of the tumors; decrease liver graft ischemia-reperfusion injury; use anti-cancer drugs; tune immunity toward liver cancer clearance. The study was published in the online August 10, 2011 American Journal of Transplantation.
Celsion Announces Publication of Clinical and Scientific Review of ThermoDox(R) as Treatment for Primary Liver Cancer
17 Aug 2011
The article “Lyso-Thermosensitive Liposomal Doxorubicin: An Adjuvant to Increase the Cure Rate of Radiofrequency Ablation (RFA) in Liver Cancer,” was published in the August 2011 issue of Future Oncology by Ronnie T.P. Poon, M.D. FRCS, Professor of Surgery, Hong Kong and Nicholas Borys, M.D., Celsion’s Chief Medical Officer. In the article, they detail the efficacy of the doxorubicin in fighting liver cancer, its increased effectiveness when coupled with hyperthermia, localization of ThermoDox (R) in tumors and tumor vasculature and rapid release of the drug when triggered by heat from the tumors themselves. The lead doctors report that they have met the enrollment objective of the Phase III HEAT study and look forward to sharing their results for interim analysis with an independent Data Monitoring Committee (DCM).
New Non-Invasive Technology Shows Promise in Shrinking Liver Tumors
14 Aug 2011
In a Phase II Study at the University of Alabama at Birmingham, 41 patients with liver cancer were treated with very low levels of an electromagnetic field emitted from a spoon-like device placed in their mouths. Boris Pasche, M.D. Ph.D., director of the UAB Division of Hematology and Oncology in the Department of Medicine, said that after six months, tumors in 14 patients had stabilized and in a female patient who had received regular therapy since August 2006, her tumor continues to shrink. No patients experienced any significant side effects. “This method literally finds cancer cells in the body and blocks their growth without affecting the growth of normal cells,” says Pasche. The therapy is ready for an FDA-registration study and randomized trials which will commence once funding is secured.
Investigators Identify Inactivating Mutations in Tumor Suppressing Gene ARID2
8 Aug 2011
Researchers at Johns Hopkins University School of Medicine have found inactivating mutations in the ARID 2 gene in 18.2% of patients with hepatitis-C Virus (HCV)-associated liver cancer. Michael S. Torbenson, M.D., and Kenneth W. Kinzler, M.D., leaders of the international team, say that their findings suggest that these mutations in the encoded ARID2 protein: “…unequivocally establish ARID2 as a liver cancer suppressor gene.” Their results are detailed in a paper titled: “Inactivating Mutations of the Chromatin Remodeling Gene ARID2 in Hepatocellular Carcinoma.”
Celsion Reaches Major Milestone with Enrollment of 600th Patient in Its Pivotal Phase III Study of Thermodox(R) in Primary Liver Cancer
3 Aug 2011
Celsion announced that it has reached its enrollment objective of 600 patients in its Phase III Heat study, a multinational, randomized, double-blind, placebo-controlled clinical trial of Thermodox(R) in combination with radio frequency ablation for the treatment of primary liver cancer. This enrollment objective ensures that the goal of the study, progression-free survival (PFS), can be achieved with adequate statistical power, with the concomitant goal of 190 PFS events. “This milestone is… a critical step toward establishing Thermodox’s(R) potential as a new standard of care in first line treatment in non-resectable primary liver cancer,” said Michael H. Tardugno, President and CEO of Celsion. The HEAT study is the largest clinical trial ever conducted in intermediate hepatocellular carcinoma (HCC).
Alnylam Completes ALN-VSP Phase I Trial in Patients with Liver Cancer
1 Aug 2011
Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, has completed its Phase I study with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement. Two genes critical for the growth and development of cancer cells are targeted in this study which was offered to patients who have failed to respond to or have tumors that have progressed after standard treatment. Out of 41 patients enrolled, several have had no tumor growth and one patient had 70% tumor regression after over a year of treatment. Alynlam presented these results at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2011.
Polaris Starts Final Study of Liver Cancer Drug
30 July 2011
Polaris Group of San Diego, a privately owned company, delivered the first dose in a Phase 3 clinical trial of its experimental cancer drug, ADI-PEG 20. The drug works by removing circulating arginine, an amino acid that liver cancer cells need to survive. Polaris plans to test the therapy in more than 600 patients in the US, Europe and Asia over the next year and a half.
Liver Cancer Linked to Metabolic Syndrome
26 July 2011
Data from a National Cancer Institute study showed that patients with metabolic syndrome had as much as a twofold increased risk of liver cancer and intrahepatic cholangiocarcinoma (ICC). Tania M. Welzel, MD, of Klinikum der J.W. Goethe-Universitat Frankfurt in Germany and NCI wrote that the study indicates metabolic syndrome is a significant risk factor for both kinds of cancer regardless of all other major liver cancer and ICC risk factors. Both diseases have increased in the U.S. and are at epidemic levels worldwide, an increase that cannot be explained completely by increased rates of hepatitis or other established causes. The study suggests that a reduction in metabolic syndrome could directly lead to a reduction in both ICC and liver cancer.
European Medicines Agency Adopts Positive Opinion for Orphan Medicinal Product Designation
26 July 2011
4SC AG, a German discovery and development company of targeted small molecule drugs for autoimmune diseases and cancer, announced that the European Medicines Agency has recommended resminostat for orphan drug designation for liver cancer. This follows the US FDA’s similar designation for the drug, an advanced compound in the fight against liver cancer. This designation give 4SC ten years of market exclusivity for the drug, direct access to centralized marketing authorization, fee reductions and protocol assistance. Resminostat modifies the DNA structure of tumor cells to cause their differentiation and programmed cell death. The drug is currently being investigated in the Phase II SHELTER study as a second-line treatment for advanced liver cancer and results are expected in 2011.
Exalenz Reports Positive Liver Cancer Diagnostic Results
24 July 2011
Exalenz Bioscience, Ltd, an Israeli company that markets systems that extract vital diagnostics from a patient’s breath, reported positive results from a preliminary trial for its BreathID, a non-invasive device that detects liver cancer. The trial was conducted at Hadassah Medical Organization’s Ein Kerem Hospital in Jerusalem where 36 patients were first checked with ultrasound. Those suspected of liver cancer underwent CT and MRI tests and 26 were found to have the disease. When tested with BreathID, the device achieved a 93 percent congruence with conventional detection methods. Exalenz is preparing clinical trials in the U.S., Israel and Canada.
WHO To Mark First World Hepatitis Day
23 July 2011
WHO marked July 28, 2011 as the first World Hepatitis Day. The day is aimed at raising awareness of the public impact of a disease that will kill 5 million people in Southeast Asia in the next 10 years. About 60% of people infected with viral hepatitis are unaware that they are infected until they show symptoms of cirrhosis or liver cancer, which may take over 20 years to develop. Viral hepatitis has killed more people than malaria, dengue and HIV/AIDS combined in the region in the last decade.
HK Experts Identify Gene That Promotes Liver Cancer Growth
20 July 2011
Researchers at the Chinese University in Hong Kong found an extraordinarily active gene called Cell Cycle-Related Kinase in liver cancer tissues of patients. The gene, normally asleep, is nudged awake by androgen receptors and generates growth of liver cells. Androgen is the male sex hormone, which explains why more men than women are afflicted by this disease. CCRK not only promotes growth of live cells, but also can transform normal liver cells into tumor cells. Alfred Cheng, research associate professor at the university’s Institute of Digestive Disease, said the CCRK gene can be a target to control, block or even prevent liver cancer growth.
Patent Profile: Multicell Technologies Receives Stem Cell Patent
14 July 2011
MultiCell Technologies, Inc. of Woonsocket, RI, a clinical-stage biopharmaceutical company focusing on unmet medical needs for the treatment of hepatic diseases, et al, announced that it had been issued a patent which is related to the isolation and use of human liver stem cells to treat liver disease. W. Gerald Newmin, Chairman and CEO of MultiCell Technologies, believes that liver stem cells can be used to reconstitute a diseased liver rather than undergo a liver transplant. He believes this could ultimately help in the fight against chronic liver disease and primary liver cancer.
Experts Find Rogue Stem Cells in Liver Cancer
7 July 2011
Liver cancers are embedded with a type of super stem cell coated with a unique surface protein called CD24. Patients with high counts of CD24 tend to have poorer chances of survival said lead researcher Irene Ng, pathology professor and director of the State Key Laboratory for Liver Cancer Research at the University of Hong Kong. Ng says that CD24 is like a switch on some cancer stem cells that activates a protein in the cell called STAT 3. STAT 3 goes into the nucleus of cells and carries out its functions which are to form tumors, spread and be drug resistant. Ng’s colleague, Terence Lee, states: “If we inhibit the function of STAT 3 we block the function of cancer stem cells.”
Cancer Patients Get Hope from Liver Trial
7 July 2011
Patients with bowel cancer that has spread to the liver are being sought in Australia, the U.S. and Europe to take part in a study that uses selective internal radiation therapy to fight the disease. Earlier results of this therapy on 325 patients in Europe showed that the treatment helped prolong the lives of half the patients with inoperable primary liver cancer an extra 10 months. 27% had intermediate liver cancer and survived an extra 17 months. Oncologist at the Royal Melbourne Hospital and Ludwig Institute for Cancer Research Associate Professor Peter Gibbs said the aim was to test how effective the treatment was in people who were also having chemotherapy. The trial is expected to be completed by mid-2012 with results published a year later.
UF Researchers See Promise in Combining Two Liver Cancer Treatments
7 July 2011
University of Florida researchers have discovered that combining doses of sorafenib with transarterial chemoembolization improved the median survival rate of patients with advanced liver cancer from 10 to 17 months. Dr. Roniel Cabrera, hepatologist and an assistant professor of gastroenterology, hepatology and nutrition in the UF College of Medicine, said the combined treatments appear to be safe with only a slight increase in the usual side effects in studies of single therapies. The findings of the study are published in the current issue of the journal Alimentary Pharmacology and Therapeutics.
Will new drugs block hepatitis C virus in its tracks?
28 June 2011
Targeted multi-drug treatments for hepatitis C patients that could stop the virus in its tracks have come a step closer, thanks to researchers at the University of Leeds, UK. The study by Dr Stephen Griffin and colleagues, published in the journal Hepatology, reveals how two prototype small molecule drugs, known as p7 inhibitors, can each attack different parts of the hepatitis C virus, which is a risk factor for liver cancer. Their findings suggest that p7 inhibitors could be a powerful way of suppressing hepatitis C, when used together with the latest generation of ‘direct-acting’ drugs.
BioAlliance Pharma Submits a Phase III Clinical Trial Application for Livatag
27 June 2011
BioAlliance Pharma is a Paris-based company dedicated to specialty and orphan oncology products. Today marks the announcement of a phase III clinical trial application for Livatag following the phase II survival data announced by BioAlliance in March 2011. This data showed a doubling of the median survival in Livatag treated patients versus patients treated with best of care transarterial chemoembolization with a cytotoxic drug. These results have been accepted for oral communication at the International Liver Cancer Association (ILCA) 2011 congress. BioAlliance has validated a new administration regimen in animal models, which significantly reduces acute pulmonary adverse events. The phase II trial had been on hold in July 2008 due to pulmonary toxicity in patients.
Earlier Diagnosis of Liver Cancer May Be Possible Via Gold Nanoparticles
26 June 2011
Promising results for a research team led by Brown University. In lab tests, gold nanoparticles ringed by a charged polymer coating are used as agents to enhance X-ray scattering signals to image tumor-like masses. The charge increased the chances that the nanoparticles would be engulfed by the cancerous cells. Nontoxic gold particles in miniscule amounts had enough critical mass to be detected by X-rays in the identification of tumor masses as small as 5mm, according to Christoph Rose-Petruck, professor of chemistry at Brown and corresponding author of the paper.
4SC Reports Data from Clinical Trials with Oral Pan-HDAC Inhibitor Resminostat
23 June 2011
German biotechnology firm 4SC reports from the ongoing oral resminostat Phase II SHELTER trial in liver cancer. After 6 weeks of study therapy, 11 out of 18 patients assessed to date show confirmed tumor stabilization. After 12 weeks of study therapy, 50% of patients assessed displayed continuous stable disease on either sorafenib and resminostat or resminostat alone. This study is expected to report Phase II results in 2011.
Gold nanoparticles help earlier diagnosis of liver cancer
22 June 2011
A research team led by Brown University reports some promising results for earlier diagnosis. In lab tests, the team used gold nanoparticles ringed by a charged polymer coating and an X-ray scatter imaging technique to spot tumor-like masses as small as 5 millimeters. The approach, detailed in the American Chemical Society journal Nano Letters, marks the first time that metal nanoparticles have been used as agents to enhance X-ray scattering signals to image tumor-like masses.
The Drug That Could
19 June 2011
Sorafenib was approved by the FDA in November 2007 for the treatment of patients with inoperable liver cancer. It is currently approved in more than 80 countries for the treatment of liver cancer. Sorafenib is a targeted mulitkinase inhibitor that decreases tumor cell proliferation and reduces blood flow to the tumor. In an international phase 3, trial known as Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP), investigators studied 602 patients looking at overall survival and symptomatic progression. The results were presented at the 43rd annual meeting of the American Society of Clinical Oncology in 2007.
Y-90 for Liver Cancer
17 June 2011
Doctors at Indiana University Medical Center in Indianapolis are offering a treatment called radioembolization for some patients with liver cancer. Matthew Johnson, M.D. Professor of Radiology and Surgery, says the radiotherapeutic drug, Yttrium-90 (Y-90), administered in microsphere form, contains a high dose of radiation that congregates around the tumor. Unlike chemoembolization, radioembolization offers the advantage, to some patients, of less fatigue, nausea, vomiting or abdominal pain. This treatment is not yet widely available in the U.S. because it requires extra training for interventional radiologists.
Lactobacillus bacteria may reduce toxicity of aflatoxins or liver cancer risk
16 June 2011
A new study suggests that some Lactobacillus bacteria may help relieve oxidative stress induced by hepatotoxins called aflatoxins, a risk factor for liver cancer. The study in the May 31, 2011 issue of Toxicology showed that ingestion of Lactobacillus casei (L. casei) or Lactobacillus reuteri (L. reuteri) helped improve a spectrum of biochemical parameters in rats exposed to alfatoxins.
Untreated hep B to send liver cancer rate soaring in Australia
5 June 2011
Deaths from liver cancer are liable to triple in the next decade, with the rise largely caused by untreated hepatitis B infections, experts say.
More than 50,000 Australians are thought to be unknowingly infected with the blood-borne virus. Without treatment, the condition can progress to liver diseases including cirrhosis or cancer.
Liver Cancer Risk Characterized in NASH Patients
1 May 2011
It has not yet been definitively established that nonalcoholic steatohepatitis can progress to liver cancer, but the evidence is mounting, Dr. Kohichiroh Yasui and colleagues reported in the May issue of Clinical Gastroenterology and Hepatology. Case reports and case series, retrospective studies, and prospective studies have all suggested such a link, but most have examined only a small number of cases and have had limited duration of follow-up. Therefore, the incidence of liver cancer among patients with nonalcoholic steatohepatitis (NASH) and the risk factors that may predispose patients with NASH to progress to liver cancer, are not yet clear. Dr. Yasui and associates performed a cross-sectional study to characterize the features of NASH in 87 Japanese patients who went on to develop liver cancer.
Blacks with liver cancer get fewer transplants
29 April 2011
African Americans with liver cancer are less likely than whites to get a transplant for the disease, according to U.S. researchers. And that gap hasn’t changed in a decade, they report in the journal Cancer. Liver cancer is a brutal disease, leaving just one in seven Americans alive five years after it has been diagnosed. About one in 100 men in the U.S. develop the cancer at some point, while women are less than half as likely to do so, according to the American Cancer Society. For the new study, Robbins and his colleagues tapped into U.S. hospital records on more than 7,700 liver cancer patients diagnosed between 1998 and 2007. All of the patients in the study had the most common form of the disease, known as liver cancer, which affects 80% of all liver cancer patients. According the U.S. Centers for Disease Control and Prevention, the liver infections hepatitis B and C are behind most cases of this type of cancer. The researchers found that over the first half of the study, white liver cancer patients had a 30 percent chance of receiving a new liver, compared to only 15 percent for blacks.
Laparoscopic Liver Resection Headed for Mainstream
11 April 2011
Laparoscopic liver resection provides significant intraoperative and postoperative benefits, compared with open hepatic resection, in patients with benign and malignant tumors and it does not compromise 5-year outcomes in liver cancer or colorectal cancer metastases, said Dr. David A. Geller, codirector of the liver cancer center at the University of Pittsburgh Medical Center. Not yet considered standard of care, “laparoscopic hepatic resection [LHR] has now been performed in more than 4,000 patients worldwide, and the benefits when compared with open hepatic resection [OHR] include decreased operating room time, less pain, less narcotic use, shorter length of stay, less blood loss when matched for size of tumor and extent of the operation performed, faster oral intake, and a Band-Aid–sized incision,” Dr. Geller concluded. The studies included meta-analyses, case cohort matched series, and single-center series from more than 20 centers.
Cirrhosis and Liver Cancer Have Risen Dramatically in Hepatitis C Patients
1 April 2011
The burden of cirrhosis, hepatic decompensation, and liver cancer has risen dramatically during the past decade among patients with chronic hepatitis C virus infection, Dr. Fasiha Kanwal and her colleagues reported in the April issue of Gastroenterology. In a large retrospective cohort study of more than 300,000 patients at Department of Veterans Affairs medical centers across the country, the prevalence of cirrhosis and hepatic decompensation doubled – and that of liver cancer increased 19-fold – between 1996 and 2006. “Thus, 1 of 5 patients with HCV had cirrhosis and 1 of 100 patients with HCV had liver cancer in the 2006 calendar year,” said Dr. Kanwal of the John Cochran division of the St. Louis VA Medical Center, and her associates.
San Diego company’s liver cancer drug reaches late testing
31 March 2011
Huge strides have been made in treating and curing many types of malignancies, but liver cancer remains a terrifying and fatal diagnosis for nearly everyone who gets it. That’s because the disease usually isn’t detected until later stages when the effects of surgery and chemotherapy are diminished. Federal regulators in 2007 approved the first drug for treating advanced forms of the cancer, but it only adds two or three months to most patients’ lives. San Diego-based Polaris Group is hoping that its lead drug candidate, ADI-PEG 20, will become the next breakthrough in treating the disease.
Nordion announces Phase III clinical trial to evaluate TheraSphere® in treatment of unresectable liver cancer
23 March 2011
Nordion Inc. announced that it has received U.S. Food and Drug Administration (FDA) approval to conduct a Phase III clinical trial for TheraSphere® under an Investigational Device Exemption (IDE). The trial will examine the safety and effectiveness of TheraSphere when the treatment is added to standard kinase inhibitor therapy in patients with unresectable liver cancer, the most common form of inoperable primary liver cancer.
The relationship between body mass index and age at liver cancer onset
15 March 2011
The incidence and mortality associated with liver cancer have been increasing worldwide, and hepatitis C virus (HCV) infection plays an important role in the pathogenesis of liver cancer. Previous studies have suggested that host factors, such as sex, alcohol consumption, smoking, diabetes mellitus, and obesity, are important risk factors for liver cancer. Meanwhile, it has been reported that HCV infection causes insulin resistance and leads to oxidative stress, potentiating fibrosis and hepatic carcinogenesis. However, the factors that influence the development of liver cancer in HCV-infected patients remain largely unknown. A research article published on February 21, 2011 in the World Journal of Gastroenterology addresses this question. The authors hypothesized that obesity influences the time to onset of liver cancer related to HCV infection, which is reflected in the patient’s age at onset. To test this hypothesis, they investigated the relationship between body mass index (BMI) and lifestyle factors and age at onset of liver cancer in HCV-infected patients.
Plasma Biomarkers Refine Risk Stratification in Liver Cancer
14 March 2011
A simple blood test may improve on systems conventionally used to estimate prognosis in patients with liver cancer, new data suggest. In a study of nearly 300 patients mainly with advanced liver cancer, baseline plasma levels of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) significantly refined the risk stratification seen with the Barcelona Clinic Liver Cancer system, researchers reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Potential New Biomarker Can Predict Cancer Metastasis
1 February 2011
A newly discovered protein variant known as carboxypeptidase E-delta N, or CPE-delta N, appears to be a powerful biomarker for predicting metastasis in patients with liver cancer, pheochromocytoma, paraganglioma, and possibly other types of cancer, a new study shows.
Predicting liver cancer spread
1 February 2011
Patients with cancer usually do not die as a result of their originally diagnosed tumor. However, many do so as a result of metastatic disease — tumors that arise at distant sites after spreading from the original tumor. Identifying biomarkers of tumor metastasis would therefore be of immense clinical benefit. In this context, a team of researchers — led by Peng Loh, at the National Institutes of Health, Bethesda; and Ronnie Poon, at the University of Hong Kong, China — has now identified a potential biomarker for predicting future metastasis in patients with the most common form of liver cancer. Specifically, the team found that quantification of the mRNA template for a truncated version of the protein carboxypeptidase E (CPE) in liver cancer patient samples predicted intrahepatic metastasis with high sensitivity and specificity. They therefore suggest that this truncated protein could be a powerful biomarker for predicting future metastasis in patients with liver cancer and thereby be of use to clinicians, helping guide therapeutic decisions.
Radiofrequency Ablation, Surgery Equal in Small Liver Cancer
31 January 2011
Overall survival is comparable for patients with small liver cancer treated with surgical resection (SR) or radiofrequency ablation (RFA), according to a study published in the January issue of Clinical Gastroenterology and Hepatology.
Complete response for advanced liver cancer during sorafenib therapy: Case Report
17 January 2011
A case that represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related liver cancer.
University of Florida doctors try to give liver cancer patients more time
12 January 2011
University of Florida physicians and researchers are looking to improve life expectancy for patients with liver cancer. Research, started in November with 120 patients with inoperable cancer, is expected to continue for a year while being funded by the only existing medication that currently treats advanced stages of liver cancer, Sorafenib.
Alnylam presents ALN-VSP Phase I trial results for liver cancer
5 January 2011
Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, today presented new clinical data from its ALN-VSP Phase I liver cancer trial in a presentation at the Dana-Farber Cancer Institute in Boston. Results from molecular analysis of human biopsy samples showed achievement of pharmacologically relevant siRNA drug levels in tissues. In addition, using a highly precise polymerase chain reaction (PCR)-based technique known as 5′- rapid amplification of cDNA ends (5′-RACE), analysis of human tissue samples showed proof of RNAi-mediated target mRNA cleavage, and thus RNAi in man with the systemically delivered RNAi therapeutic. These results provide significant human proof of concept for Alnylam’s efforts in advancing RNAi therapeutics to patients.