STANFORD, Calif. – A new drug has been shown to be effective in treating and preventing the most common cancer in the United States: basal cell carcinoma skin cancer, according to a new study in the New England Journal of Medicine to be published June 7.
The drug, vismodegib (trade name: Erivedge), was tested in a clinical trial in patients with Gorlin syndrome, a rare disease in which individuals have tens to hundreds of disfiguring basal cell carcinoma tumors.
The findings are being released in conjunction with two other papers in the same journal issue that show the effectiveness of vismodegib in treating BCCs that are advanced or metastatic.
All three articles include authors from the Stanford University School of Medicine.
"It is a landmark day for patients with basal cell carcinoma and all those involved in their care – the greatest advance in therapy yet seen for this disease," writes John Lear, MD, in an accompanying editorial.
Lear is a consultant dermatologist at Manchester Royal Infirmary and the Dermatology Centre of Hope Hospital in Manchester, UK.
The research is being published five months after vismodegib became the first drug in its class to gain approval from the U.S. Food and Drug Administration.
Vismodegib, which was developed by the biotech firm Genentech/Roche, targets a molecular signaling pathway in cells called the Hedgehog signaling pathway.
The drug works by inhibiting the Hedgehog pathway, which is inappropriately activated in basal cell carcinomas.
While the pathway is important in early embryonic development, it is generally inactive in healthy adults.
In January, the FDA approved the drug for use in treating advanced forms of basal cell carcinoma.
In the study of the drug's effect on patients with Gorlin syndrome (also known as Basal Cell Nevus Syndrome) the researchers showed that subjects taking vismodegib developed an average of two new tumors per year, compared with 29 new tumors in subjects taking placebo. The drug is taken daily in a pill form.
This investigator-initiated, double-blind placebo trial involved 41 patients with Gorlin syndrome and was stopped early due to the overwhelming effectiveness of vismodegib, the article states. It was considered unethical not to offer the drug to those participants taking a placebo.
"How often in your life do you get to have worked within a field where you finally get to test to a drug that actually changes people's lives?" said Jean Tang, MD, PhD, assistant professor of dermatology at Stanford and first author of the study. "We were very excited about the results."
She added: "In most subjects, all the carcinomas clinically disappeared. No tumors progressed while the subjects took vismodegib."
Currently there is no good treatment for Gorlin syndrome, which afflicts one in 50,000 people; these individuals often develop their first BCC tumor in childhood.
The constant growth of BCC tumors, while generally non-lethal, can be treated surgically but the persistent operations leave scarring, and some BCC tumors can eventually become inoperable.
"These patients usually have severe scarring by the time they reach adulthood," Tang said. "The cancer generally doesn't kill you, but obviously it affects the quality of life. Many patients never marry, never have families, they face more limited job opportunities. There currently are no good treatment options."
The drug did not permanently cure patients of their tumors, as the BCC tumors returned once the treatment was stopped, although very slowly.
Side effects include mild taste loss, muscle cramps, mild hair loss and weight loss, and discontinuation rates by patients were high.
Tang previously worked as a postdoctoral scholar with the senior author of the study Ervin Epstein, MD, at Children's Hospital of Oakland Research Institute.
About 2.8 million U.S. patients are diagnosed each year with basal cell carcinoma, which is generally caused by sun exposure and cured by surgical removal or radiation treatment.
But in rare cases, known as locally advanced disease, the tumorous lesions invade nearby tissues and can become disfiguring or even metastasize and spread elsewhere in the body. It is rarely fatal, but can be painful and lead to other complications.
The second of the three papers presents the findings from the phase-2 Genentech-sponsored clinical trial that were the basis for the FDA's decision to allow vismodegib to be used to treat advanced forms of BCC in adults.
The drug was successful 43 percent of the time in either complete or partial shrinkage of tumors in the 96 patients with advanced disease who participated in the trial, the study reports.
In the third article – a letter to the editor detailing a case study of a 41-year-old man who had skin cancers all over his body caused by a unique genetic mutation in the Hedgehog pathway different from Gorlin syndrome – the cancer still responded well to vismodegib.
This suggests that Hedgehog-inhibiting drugs like vismodegib could be successful in treating a variety of other invasive cancers caused by abnormalities in the pathway, said Anthony Oro, MD, PhD, senior author of the letter and a professor of dermatology at Stanford.
The publication of the papers is a milestone in what has been a global effort to develop a new cancer treatment that can be traced back about 16 years.
That's when biologists, including a group led by Epstein and Stanford professor of developmental biology Matthew Scott, PhD, first linked the Hedgehog pathway to human cancer.
Since that initial discovery, scientists have been intensely studying the pathway searching for drugs that can treat cancers by blocking it.
Now that one drug has been found, there are five or six other companies developing similar drugs, each of which may benefit patients, Oro said.
"We now have a brand new class of drugs that can treat these cancers," Oro said. "As a dermatologist, this is exciting to see. There is nothing for these patients that works. Their cancers are often surgically inoperable."
The drug also comes with a boxed warning of the potential risks of death and of severe birth defects to unborn babies. It costs $7,500 per month. The duration of treatment per patient is expected be around 10 months.
A study led by Karolinska Institutet in Sweden reports for the first time the positive effects of an active vaccine against Alzheimer's disease.
The new vaccine, CAD106, can prove a breakthrough in the search for a cure for this seriously debilitating dementia disease.
The study is published in the distinguished scientific journal Lancet Neurology.
Alzheimer's disease is a complex neurological dementia disease that is the cause of much human suffering and a great cost to society.
According to the World Health Organization, dementia is the fastest growing global health epidemic of our age.
The prevailing hypothesis about its cause involves APP (amyloid precursor protein), a protein that resides in the outer membrane of nerve cells and that, instead of being broken down, form a harmful substance called beta-amyloid, which accumulates as plaques and kills brain cells.
There is currently no cure for Alzheimer's disease, and the medicines in use can only mitigate the symptoms.
In the hunt for a cure, scientists are following several avenues of attack, of which vaccination is currently the most popular.
The first human vaccination study, which was done almost a decade ago, revealed too many adverse reactions and was discontinued.
The vaccine used in that study activated certain white blood cells (T cells), which started to attack the body's own brain tissue.
The new treatment, which is presented in Lancet Neurology, involves active immunization, using a type of vaccine designed to trigger the body's immune defense against beta-amyloid.
In this second clinical trial on humans, the vaccine was modified to affect only the harmful beta-amyloid.
The researchers found that 80 percent of the patients involved in the trials developed their own protective antibodies against beta-amyloid without suffering any side effects over the three years of the study.
The researchers believe that this suggests that the CAD106 vaccine is a tolerable treatment for patients with mild to moderate Alzheimer's.
Larger trials must now be conducted to confirm the CAD106 vaccine's efficacy.
Read the scientific article at http://goo.gl/Id9uU .
SAN FRANCISCO – A simple eye test may someday offer an effective way to identify patients who are at high risk for stroke, say researchers at the University of Zurich.
They showed that a test called ocular pulse amplitude (OPA) can reliably detect carotid artery stenosis (CAS), a condition that clogs or blocks the arteries that feed the front part of the brain. It's a known risk factor for stroke.
The OPA test could be performed by ophthalmologists – physicians who treat eye diseases – during routine exams.
The study, which is published in the June issue of Ophthalmology, the journal of the American Academy of Ophthalmology, confirmed that patients who had the lowest OPA scores also had the most seriously blocked arteries.
Each year, approximately 795,000 Americans suffer a new or recurrent stroke, and more than 137,000 of these people die as a result. People with severe CAS are much more likely to suffer stroke.
Physicians would like to catch and treat CAS before that can happen, but because CAS has no symptoms and an efficient test is not currently available, the disease often goes undetected.
The Swiss research team used a device called the dynamic contour tonometer to check the OPA of 67 patients who were assumed to have CAS.
The OPA score is calculated by finding the difference between the two pressure levels that occur inside the eye during the two phases of the heartbeat − the systolic and diastolic. The tonometer measures the two pressure levels, then instantly computes the patient's OPA score.
When blood flow to the eye is blocked by CAS, there is not much difference between the two pressure levels, so the OPA score is low.
The study confirmed that patients with the lowest OPA scores also had the most seriously blocked arteries. The researchers used ultrasound exams to corroborate that each study participant had CAS and to detail the severity of his or her blockage.
"Our results show that ocular pulse amplitude is a reliable, safe screening test for carotid artery stenosis," said lead researcher Pascal Bruno Knecht, M.D. "We recommend further study to confirm the value of using OPA to detect and assess the severity of CAS and to define its use in stroke prevention."
A research review performed for the U.S Preventive Services Task Force indicated that if an efficient screening test for CAS were available, the incidence of stroke and fatalities due to stroke could be substantially reduced.
The review stated that the test should be able to detect clinically significant CAS, defined as 60 percent to 99 percent blockage of the carotid arteries.
Some high-tech tests, such as magnetic resonance angiography and color duplex ultrasound, already meet this standard, but they are expensive and not widely available. Their primary use is in diagnosing patients who already have symptoms of stroke.
It could be efficient to perform the OPA test during a standard eye exam, if the ophthalmologist is already using the dynamic contour tonometer to screen for glaucoma.
This type of tonometer is not widely used in the United States, although it is in Europe.
The researchers say that other than CAS, very few diseases could cause low OPA scores, and that an ophthalmologist could easily rule out these other diseases during an eye exam.
California Health and Human Services Agency Secretary, Diana S. Dooley announced Monday the members appointed to the Let’s Get Healthy California Task Force and the Expert Advisors charged with developing a 10-year plan to make Californians healthier.
The appointments are made pursuant to Governor Edmund G. Brown, Jr.’s Executive Order.
The task force will be co-chaired by Secretary Dooley and Don Berwick, MD MPP who is a senior fellow at the Center for American Progress, is the former president and CEO of the Institute for Healthcare Improvement and served by appointment of President Obama as the Administrator of the Centers for Medicare and Medicaid Services until December, 2011.
“With the leadership of Dr. Don Berwick and California’s world-class talent in health, technology, education and research, it wasn’t hard to assemble this energetic group of leaders for our work ahead,” said Secretary Dooley. “With the knowledge, diversity and experience of these appointees and the support of so many others committed to our success, I look forward to receiving an innovative plan to reduce the burdens of chronic and preventable diseases and improve the health of all Californians.”
The Task Force and the Expert Advisors will work together to gather, evaluate and prioritize the best ideas and practices and organize them into a 10-year plan to improve quality, control costs, promote personal responsibility for individual health, and advance health equity.
The report will establish baselines for key health indicators, identify obstacles, inventory best practices, provide fiscally prudent recommendations and create a sensible framework for measuring improvements in key areas including:
The first meeting of the Task Force will be held in Los Angeles on June 11, 2012. The plan will be presented by December 15, 2012. The members of the Task Force and the Expert Advisors are below.
Let’s Get Healthy California Task Force
Co-Chairs
Don Berwick, MD, MPP, Senior Fellow, Center for American Progress. Dr. Berwick is the former President and CEO of the Institute for Healthcare Improvement and served by appointment of President Obama as the Administrator of the Centers for Medicare and Medicaid Services until December, 2011.
Diana Dooley, Secretary, California Health and Human Services Agency. Prior to her appointment by Governor Jerry Brown, Ms. Dooley was President and CEO of the California Children’s Hospital Association.
Members
Dr. America Bracho, MPH, CDE, Executive Director, Latino Health Access, Santa Ana. Dr. Bracho is recognized as a local, regional and national expert in the area of Latino health issues, health education, minority women, cultural competency, community organizing, diabetes education and HIV.
Lloyd Dean, President and CEO, Dignity Health (formerly Catholic Healthcare West). Mr. Dean is responsible for overall management, strategy and direction of Dignity Health’s hospitals, ancillary services, home health care and medical group foundations. He is a frequent national speaker and has received numerous awards for his healthcare leadership.
Susan Desmond-Hellmann, MD, MPH, Chancellor, University of California, San Francisco. Dr. Desmond-Hellman is an accomplished scientist, researcher and educator who previously served as president of product development at Genentech. In 2009, Forbes magazine named her as one of the world’s seven most “powerful innovators,” calling her “a hero to legions of cancer patients.”
George Halvorson, Chairman and CEO, Kaiser Permanente. As the leader of the nation’s largest nonprofit health plan and hospital system, Mr. Halvorson has won many awards for his commitment to health technology and quality improvement and has written extensively on the U.S. health care system.
James T. Hay, MD, President, California Medical Association. Dr. Hay is a family physician at the North Coast Family Medical Group in San Diego and has been actively engaged as a champion and advocate for improved medical practice.
Ed Hernandez, O.D., State Senator, Chair, Senate Committee on Health. As a practicing optometrist in private practice, Senator Hernandez is pragmatic and innovative in his approach to addressing health and health care policy.
Mitch Katz, MD, Director, Los Angeles County Department of Health Services. Prior to his tenure with Los Angeles County, Dr. Katz was the head of the San Francisco public health department and is a widely recognized and respected provider of health services through public and community action.
Pam Kehaly, President and General Manager, Anthem Blue Cross of California. Ms. Kehaly is responsible for the management of local group insurance business in California. Through Anthem Blue Cross and its foundation, she is engaged in the fight against the childhood obesity epidemic, including a pilot program that will bring fresh fruit and vegetables to schools in underserved communities.
Kenneth W. Kizer, MD, MPH, Director, Institute for Population Health Improvement, University of California Davis Health System and Distinguished Professor, UC Davis School of Medicine and Betty Irene Moore School of Nursing. Prior to Dr. Kizer’s launch of the new Institute he was founding President and CEO of the National Quality Forum. Previously, as Undersecretary of Health, U.S. Department of Veterans Affairs, he was chiefly responsible for the transformation of the VA healthcare delivery system.
Richard Levy, PhD, Chairman of the Board, Varian Medical Systems, Inc., the world’s leading manufacturer of medical devices and software for treating cancer and other medical conditions. Dr. Levy has been a leader in his company and with the Silicon Valley Leadership Group in the active and effective engagement of employees in their own health.
Bob Margolis, MD, Managing Partner and CEO, HealthCare Partners. Dr. Margolis has been an innovator in the managed care industry for more than 20 years and is a well-regarded health expert because of his leadership in quality improvement, integrated delivery systems and physician practice management.
Joy Melnikow, MD, MPH, Director, Center for Healthcare Policy and Research and professor of medicine, Department of Family and Community Medicine, University of California, Davis. Dr. Melnikow is a family physician and researcher who contributes on many state and national policy groups including the U.S. Preventive Services Task Force to address policies to improve health outcomes, taking into consideration patient preferences and decision making, cost-effectiveness, underserved populations, and health disparities.
Arnold Milstein, MD, Professor, Stanford University’s Clinical Excellence Research Center. Dr. Milstein leads this collaboration of the Schools of Medicine, Engineering, and Business to design and test new health care delivery models to lower per capita health care spending and improve clinical outcomes. He also serves as the Medical Director of the Pacific Business Group on Health, the largest business coalition on health care improvement in the U.S.
Bill Monning, Assembly Member, Chair of the Assembly Committee on Health. Prior to his state service, Assemblyman Monning was a professor at the Monterey College of Law and a professor of International Negotiation and Conflict Resolution at the Monterey Institute of International Studies. He is a leading champion of preventive medicine.
Ed Moreno, MD, MPH, Director and Health Officer, Fresno County Department of Public Health and President, Health Officers Association of California. In addition to his County service, Dr. Moreno teaches resident physicians at the Fresno campus of the University of California, San Francisco and is actively engaged to reduce health disparities in the San Joaquin Valley.
Steven Packer, MD, President and CEO, Community Hospital of the Monterey Peninsula, and Board Chair, California Hospital Association. Dr. Packer has been actively engaged in public policy and advocacy in furtherance of quality improvement and care delivery reforms.
Dave Regan, President, Service Employees International Union – United Healthcare Workers - West. Mr. Regan is a political and healthcare reform activist with 20 years of leadership in the labor movement who is deeply committed to improving healthcare quality, lowering costs and forging new relationships to foster health.
Joe Silva, Superintendent, Tuolumne County Office of Education and past president, California County Superintendents Education Services Association. Mr. Silva is a tireless advocate of children, believes in the importance of physical fitness, created a highly successful anti-obesity campaign and recently received a lifetime achievement award from the Association of California School Administrators.
Anne Stausboll, JD, CEO, California Public Employees Retirement System (CalPERS). Prior to leading CalPERS, Ms. Stausboll was Chief Deputy State Treasurer. As one of the single largest purchasers of healthcare, CalPERS has a significant stake in the triple aim of improving healthcare, lowering cost and promoting health.
Kelly Traver, MD, Founder and CEO, Healthiest You Corporation and the author of The Program, based on her research on the human brain and its resistance to change. Before founding her current company, which works with employers to empower and engage employees in their own health, Dr. Traver was Global Medical Director for Google.
Kerry Tucker, Principal, Nuffer, Smith, Tucker, Inc., Member, California State Board of Food and Agriculture. As a public relations professional, Mr Tucker has worked extensively with national and California agri-food clients and with the California Institute of Food and Agricultural Research, where he founded Food Foresight, the first issue anticipation system exclusively for the field of food and agriculture.
Antronette “Toni” Yancey, MD, MPH, Professor and Co-Director, UCLA Department of Health Services Center to Eliminate Health Disparities within the School of Public Health. Dr. Yancey is a renowned expert on chronic disease prevention. She serves on the Institute of Medicine Standing Committee on Childhood Obesity Prevention, Health Literacy Roundtable, and National Physical Activity Plan Steering Committee.
Expert Advisors to the Let’s Get Healthy California Task Force
Honorary Chair
Robert K. Ross, MD, President and CEO, The California Endowment. As a pediatrician, a member of the California Health Benefit Exchange and a passionate advocate for improving health, Dr. Ross has led many efforts directly related to the Governor’s Let’s Get Healthy Order, including Building Healthy Communities and Health Happens Here.
Members
Ann Boynton, Deputy Executive Officer for Benefit Programs, Policy and Planning, California Public Employees Retirement System (CalPERS). Ms. Boynton is a recognized expert in health care policy and health care information technology issues.
Nadine Burke Harris, MD, MPH, Founder and CEO, Center for Youth Wellness. Dr. Burke runs this San Francisco-based comprehensive health and wellness center that integrates medical, mental health, holistic and social services for an evidence-based approach to improving the health and well-being of urban children and youth.
Sophia Chang, MD, MPH, Director, California HealthCare Foundation’s Better Chronic Disease Care program, which focuses on improving clinical outcomes and quality of life for Californians with chronic diseases. Dr. Chang was previously the director of the Veterans Health Administration’s Center for Quality Management in Public Health.
Molly Coye, MD, MPH, Chief Innovation Officer, UCLA Health System. Dr. Coye is an internationally recognized leader in advancing innovative approaches to healthcare delivery, adopting new technologies and shaping national health policy.
Patricia “Pat” Crawford, DrPH, RD, Co-founder and Director, Atkins Center for Weight and Health, CE Nutritional Specialist, and Adjunct Professor, University of California, Berkeley. Dr. Crawford has conducted extensive research in the prevention of childhood obesity. She is currently leading studies evaluating the impact of programs and policies to improve the foods in California schools and is on the Institute of Medicine’s Standing Committee on Childhood Obesity Prevention.
Steve Fields, MPA, Executive Director, Progress Foundation. Mr. Fields was a member of the President’s Commission on Mental Health Task Panel on deinstitutionalization, rehabilitation and long-term care. He has served three terms as the president of the California Association of Social Rehabilitation Agencies.
Deborah “Debbie” Freund, PhD, MPH, President, Claremont Graduate University. Dr. Freund is an internationally-recognized health economist, known in particular for her research in the areas of Medicaid and health care outcomes.
Alan Glaseroff, MD, Director, Stanford Coordinated Care. Dr. Glaseroff was previously the chief medical director for the Humboldt-Del Norte IPA and is nationally known for his innovations in the areas of primary care design, diabetes and self-management. He was named California Family Physician of the Year in 2009.
Neal Halfon, MD, MPH, Director, UCLA Center for Healthier Children, Families and Communities, and Professor of Pediatrics, Health Services and Public Policy. Dr. Halfon is an internationally recognized expert on children’s health, health care, and health policy. He currently directs the Health Measurement Network for the National Institute of Health funded National Children’s Study, and the Life Course Research Network for the federal Maternal and Child Health Bureau.
Richard “Dick” Jackson, MD, MPH, Professor and Chair, Environmental Health Sciences, UCLA School of Public Health. Dr. Jackson has done extensive work on the impact of the environment on health, particularly in children. He also chaired the American Academy of Pediatrics Committee on Environmental Health.
Elizabeth “Beth” McGlynn, PhD, Director, Kaiser Permanente’s Center for Effectiveness and Safety Research. Dr. McGlynn is an internationally known expert on methods for evaluating the appropriateness and quality of health care delivery. She is a member of the Institute of Medicine and serves on several boards and national advisory committees.
Lenny Mendonca, MBA, Senior Partner, McKinsey & Company, San Francisco. Mr. Mendonca has helped dozens of government, corporate and not-for-profit clients solve their most difficult management challenges and has written and spoken extensively on health care issues. He is chair emeritus of the Bay Area Council and is chair of the Economic Institute of the Bay Area.
Mary Pittman, DrPH, President and CEO, Public Health Institute (PHI). Dr. Pittman is a nationally recognized leader in improving community health, addressing health inequities among vulnerable people and promoting quality of care. Her overarching goal is for PHI to become known for leadership in creating healthier communities.
Wells Shoemaker, MD, Medical Director, California Association of Physician Groups and co-chair California Quality Collaborative. Dr. Shoemaker has implemented successful programs across California to address health disparities, improve diabetes care and create employee wellness plans.
Steve Shortell, PhD, MPH, MBA, Blue Cross of California Distinguished Professor of Health Policy and Management and Dean, School of Public Health at the University of California, Berkeley. A leading health care scholar, Dr. Shortell has done extensive research identifying the organizational and managerial correlates of quality of care and of high performing health organizations. He is an elected member of the Institute of Medicine of the National Academy of Sciences and is helping lead a number of initiatives to improve individual and community health.
Anthony Wright, Executive Director, Health Access. Mr. Wright is a leading voice for health care consumers in California, and since 2002, he has led the statewide health care consumer advocacy coalition for quality, affordable care for all Californians.
Ellen Wu, MPH, Executive Director, California Pan-Ethnic Health Network. Ms. Wu serves on numerous boards and advisory committees including the Managed Risk Medical Insurance Board, the California Budget Project and Oakland’s Parks and Recreation Advisory Commission. She also teaches health policy and public health at San Francisco State University.