SciQuest.org

#1 Doctor: Resolve to let patient speak without interruption and describe their symptoms.
Patient: Resolve to focus on the problem I am seeing the doctor about and not come with a list of 10 complaints for a 15 minute visit.

#2 Doctor: Resolve to keep a pleasant tone of voice when answering night and weekend calls from the answering service or nurses.
Patient: Resolve to get my prescriptions filled during office hours, not forget my medications while traveling and to use nights and weekend phone calls for emergencies only.

#3 Doctor: Resolve to exercise a minimum of 4 times a week for better health.
Patient: Ditto

#4 Doctor: Resolve to train my staff and model excellent customer service for patients.
Patient: Resolve to understand that getting an instant referral, prescription, note for jury duty, letter to my insurance from the doctor is not my god-given right and I will stop bitching.

#5 Doctor: Resolve to give at least one compliment a day to my office staff, child and spouse.
Patient: Ditto

#6 Doctor: Resolve to apologize when I am late seeing a patient who has been waiting.
Patient: Resolve to not complain when the doctor is late because I understand that another human being needed attention. It might me me in the future who needs extra time.

#7 Doctor: Resolve to do one new thing a month that is novel that I would put off ( a play? travel? special activity with a child or spouse? computer skill? music? see a friend?)
Patient: Ditto

#8 Doctor: Resolve to review all insurance payers and drop contracts that are not paying market rates for my skills and education. I will not go bankrupt.
Patient: Resolve to try and understand the medical economics that require my doctor to drop my insurance. If my doctor isn’t worth paying a little more for the visit I will find a new doctor.

#9 Doctor: Resolve for each new prescription I write I will explain 5 things. The name of the medication. The reason for the medication. The side effects. How to take it. And how long to take it.
Patient: Once the doctor has prescribed a medication, I will take it as prescribed.

#10 Doctor: I will give thanks that I have a wonderful profession where I can help people in a special way.
Patient: I will not underestimate the many years of training and sacrifice my doctors have gone through and I will appreciate that they are trying their hardest to help me stay healthy.

Inhibiting the growth of blood vessels that supply tumors slows the progression of metastatic breast cancer according to results of a large clinical trial of Avastin, an anti-angiogenic therapy. The study, published in the December 27th issue of the New England Journal of Medicine, found that Avastin in combination with chemotherapy significantly prolongs progression-free survival for women with breast cancer compared to chemotherapy alone.

Rush University Medical Center participated in the clinical trial which was sponsored by the National Cancer Institute and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).

The study of 722 women with recurrent (metastatic) breast cancer found that the women who received Avastin in combination with standard chemotherapy had a doubling of delay in worsening of their cancer by approximately five months, on average, compared to patients treated with chemotherapy alone. Those on Avastin had progression-free survival of 11.3 months compared to 6 months on standard chemotherapy alone.

“This therapy is a one-two punch! You hit the tumor with the chemo and sabotage new blood vessel growth by restricting its oxygen supply with Avastin,” said Dr. Melody Cobleigh, co-author of the study and director of the Coleman Foundation Comprehensive Breast Center at Rush. “This is a noteworthy advance in cancer treatment.”

Avastin is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis and the maintenance of existing blood vessels throughout the lifecycle of a tumor. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor’s ability to grow and spread in the body.

Avastin not only slowed the growth of the tumor, it also doubled the remission rate (the shrinkage of tumors by 50 percent or more) compared with chemotherapy alone. With chemotherapy, 25% of tumors responded; with the combination of chemotherapy and bevacizumab, 49% did so.

Rush University Medical Center has been involved in the study of Avastin from the very beginning, participating in the Phase I, Phase II and Phase III studies of the drug. The next step is studying the drug in the adjuvant setting to determine if it can help decrease the risk of cancer recurrence.

“The tumor can’t grow bigger than the size of a sesame seed without an oxygen supply,” said Cobleigh. “And patients can stay on Avastin as long at it works. It is not a chemotherapy drug so it has minimal toxicity. “

According to the American Cancer Society, an estimated 178,000 women will be diagnosed with breast cancer and approximately 40,000 will die from the disease in the United States in 2007.

Rush University Medical Center

Patients with severe COPD may benefit more from therapy that combines salmeterol and fluticasone [SFC] than treatment with tiotropium, according to results from a long-term, multi-center study, “Investigating New Standards for Prophylaxis in Reducing Exacerbations” (INSPIRE) that directly compared the two therapies.

“Although we found no difference in the overall rate of exacerbations between treatment groups, SFC treatment was associated with better health status, fewer patient withdrawals, and a lower mortality rate than occurred during tiotropium therapy,” said lead author if the study, Jadwiga Wedzicha, M.D., of the Royal Free & University College Medical School in London

This was the first large-scale trial to directly compare the two different treatment approaches. The results appeared in the first issue for January of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

The researchers recruited 1,323 patients with severe COPD and randomized them to receive one of two treatments either SFC or tiotropium for two years. They analyzed number and type of exacerbations, health status as measured by the St. George’s Respiratory Questionnaire (SGRQ), lung function (post-dose forced expiratory volume in one second) and study withdrawal rate. The study was double-blinded and double-dummy controlled, and all patients underwent identical intensification of treatment before beginning the trial to standardize their clinical conditions.

While exacerbation rates between the two treatment groups were statistically indistinguishable, there were differences in the treatment that the exacerbations required. Oral corticosteroids were used more often to treat the tiotropium group, whereas patients on SFC required antibiotics more frequently.

“This finding provides indirect evidence that these treatments affect apparently similar patients in different ways that affect clinical judgment,” wrote Dr. Wedzicha in the article. “This difference warrants further study to determine the factors that affect therapeutic choice.”

There was also a small but statistically significant improvement in the SGRQ scores for patients on SFC. While this difference did not reach the standard of clinical significance, it did indicate that overall, SFC patients experienced a slightly higher overall quality of life and a post-hoc analysis revealed that more patients on SFC had a clinically significant improvement in health status than those on tiotropium therapy

Most strikingly, mortality was significantly lower in the SFC group during the study period, even though the trial was not powered to detect such a difference. There was more than a 50 percent reduction in the risk of on-therapy all-cause death at any time during the study period for the SFC patients. Patients undergoing SFC treatment were also significantly less likely to withdraw from the trial than others.

“Our study raises several important questions,” noted Dr. Wedzicha. “Why is there a difference between treatments? What is the biological basis of the differential effect on exacerbations, and is it related to the difference in mortality between the two treatments?”

Despite no difference in the overall rate of exacerbations between treatment groups, SFC treatment was associated with better health status, fewer patient withdrawals, and a lower mortality rate than occurred during tiotropium therapy and this may have important implications for the clinical management of COPD.

American Thoracic Society (ATS)
61 Broadway
New York, NY 10006
United States
http://www.thoraci

Researchers at the Ireland Cancer Center of University Hospitals Case Medical Center are the first in the region to have joined a nationwide clinical trial to evaluate the effectiveness of a gene therapy in patients with advanced melanoma which is aimed to help a patient’s own immune system fight their cancer. The gene therapy is termed Allovectin-7®, and is injected directly into the cancer while it is still in the body in order to make it appear foreign to the immune system. Previous studies using the gene therapy have shown that injection of a single site of cancer can train the immune system to fight other areas of the disease in the body which have not been injected with the gene.

“Cancer cells often hide from the body’s natural disease-fighting mechanisms because they arise from normal tissue and don’t appear as foreign to the immune system,” said Julian Kim, MD, Chief of Surgical Oncology and lead investigator of the study at University Hospitals Case Medical Center. “The challenge in treating advanced melanoma is to find a way to train the patient’s immune system to recognize cancerous cells as foreign which will help to eliminate them. The concept of injecting a gene into a cancer to make it appear as a foreign tissue essentially creates a personalized vaccine for each individual patient’s cancer. The hope is that the newly formed cancer vaccine will trigger several of the body’s natural immune response mechanisms to recognize and attack the cancer, both within the injected cancer and throughout the body.”

The current Allovectin-7® study is focused upon patients who have advanced stages of the skin cancer termed melanoma. Melanoma is among the fastest-growing cancer diagnoses, with the number of new cases rising at a 3 to 5 percent annual rate during the last 30 years. Although early detection of melanoma results in many patients being cured by surgical removal of the melanoma, in a percentage of patients the disease will spread to other areas of skin or organs. The American Cancer Society estimates that in 2007 about 60,000 new cases of melanoma will be diagnosed in the United States and more than 8,000 patients will die from melanoma, suggesting that new treatments such as gene therapies and vaccines are needed.

University Hospitals Case Medical Center is the only regional center participating in the gene therapy trial and has joined 40 other melanoma centers nationwide to complete the study. Co-investigators at UHCMC include Henry Koon, MD, and CJ Nock, MD. The current study is a Phase III clinical trial, where patients are randomly assigned to be treated with either the Allovectin-7® gene therapy or traditional chemotherapy. Allovectin-7® has been previously administered to over 700 cancer patients in several multi-center clinical trials prior to the start of this study. To find out more information about this clinical trial or others at the Ireland Cancer Center, patients are encouraged to first visit http://www.melanomatrial.com. Patients can also call 1-800-641-2422 or visit the website http://www.irelandcancercenter.org.

“The Ireland Cancer Center aims to bring the newest therapies to our patients and this new study is a prime example of bringing the latest research into our clinical practice,” says Stanton Gerson, MD, Director of the Ireland Cancer Center. “We are pleased to be able to offer this innovative gene therapy trial to patients in the Northeast Ohio region.”

About University Hospitals

With 150 locations throughout Northeast Ohio, University Hospitals serves the needs of patients through an integrated network of hospitals, outpatient centers and primary care physicians. At the core of our Health System is University Hospitals Case Medical Center. The primary affiliate of Case Western Reserve University School of Medicine, University Hospitals Case Medical Center is home to some of the most prestigious clinical and research centers of excellence in the nation and the world, including cancer, pediatrics, women’s health, orthopedics and spine, radiology and radiation oncology, neurosurgery and neuroscience, cardiology and cardiovascular surgery, organ transplantation and human genetics. Its main campus includes the internationally celebrated Rainbow Babies & Children’s Hospital, ranked best in the Midwest and first in the nation for the care of critically ill newborns; MacDonald Women’s Hospital, Ohio’s only hospital for women; and Ireland Cancer Center, which holds the nation’s highest designation by the National Cancer Institute of Comprehensive Cancer Center.

University Hospitals

Contrary to previous studies, married patients with lung cancer do not have longer survival, according to analysis of an extensive Mayo Clinic database in the December issue of “The Oncologist.”

However, the results suggest some other potentially important differences among patient subgroups — including the possibility that married patients receive a more aggressive approach to lung cancer treatment, write Dr. Aminah Jatoi and colleagues.

The researchers analyzed data on nearly 5,900 patients from a Mayo Clinic database of patients with non-small cell lung cancer (NSCLC), the most common type of lung cancer. The database included information on a wide range of factors, including cancer stage, cancer treatment, and other factors affecting prognosis.

The study also included information on marital status: 76 percent of the patients were married (average age, 65 years), four percent single, seven percent divorced, and twelve percent widowed (average age, 73 years). The researchers analyzed the data to see if there was any relationship between the patients’ marital status at the time their cancer was diagnosed and their survival outcomes.

Initial analysis found no significant differences in survival among the different marital status groups. This remained true after adjustment for important prognostic factors, including age, tumor stage, and smoking. The results were in contrast to previous studies suggesting that married patients with lung cancer tended to have longer survival.

However, exploratory analyses found some significant differences in lung cancer treatment by marital status. Widowed and divorced patients received less aggressive treatment for cancer, which in some cases seemed to lead to shorter survival times. Survival was also shorter for patients in certain subgroups — for example, widowed patients with stage IA lung cancer (the least advanced stage).

Some aspects of quality of life also differed among marital groups. Divorced patients had greater financial concerns than patients in the other groups, while married and widowed patients had greater spirituality and better social support.

Smaller, less well-controlled studies have reported longer survival for married patients with lung cancer. The extensive Mayo Clinic NSCLC database provided an opportunity to re-evaluate the relationship between marriage and lung cancer survival.

The findings show no differences in survival based on marital status. “Nonetheless, marital status at times appeared to have influenced whether or not a patient received certain types of cancer therapy,” the researchers write.

The subgroup analyses also suggest other differences in lung cancer treatment and quality of life that are worthy of further exploration, Dr. Jatoi and coauthors believe. They conclude, “Thus, health care providers should continue to remain sensitive to the importance of human bonds as they care for patients with NSCLC.”

The new article, entitled “Does Marital Status Impact Survival and Quality of Life in Patients with Non-Small Cell Lung Cancer? Observations from the Mayo Clinic Lung Cancer Cohort,” is available online at http://theoncologist.alphamedpress.org and in print in the December issue of “The Oncologist.”

About AlphaMed Press

AlphaMed Press publishes the internationally renowned journals “Stem Cells” and “The Oncologist.” “Stem Cells,” now in its 25th year, is the oldest and one of the world’s top-tier peer-reviewed monthly journals in the fast-paced area of stem cells and regenerative medicine. “The Oncologist,” in its 12th year, is a premier peer-reviewed monthly journal dedicated to physicians entrusted with the care of cancer patients. Its highly acclaimed CME program, “The Oncologist CME Online,” has awarded more than 32,800 AMA PRA Category 1 Credits(TM). View AlphaMed Press journals at http://www.alphamedpress.org.

AlphaMed Press
http://www.alphamedpress.org

I read an article in Time Magazine from a Dr. Haig who couldn’t tolerate a patient who “googled” him, her health conditions and treatments. It made me stop and think about patients who “google”. They often send me articles they have discovered about their illness or bring information they have downloaded. Many times the information is not exactly evidence based nor well researched. There are a plethora of experts with “Doctor” in front of their name that tout research that was published in an obscure journal. Other times it is anecdotal or advertisements. The internet can be a wonderful thing but one needs the ability to sift through the junk. When it comes to health, that is my role.

Despite the fact that there is very little a patient can bring me that I don’t already know…I don’t disdain the effort. An involved patient is one I can work with. I try to show respect for whatever product or treatment they are asking about but I don’t hesitate to give “the other side of the story” if there is evidence against it. Many times it wont hurt anything but their pocketbook and I tell them so.

Here is what I don’t like, however. I don’t like it when a patient wants me to research something obscure. If they have heard of a new medication or treatment that is not yet proven, I ask them to get the information and I’ll review it. According to a recent study in Annals of Internal Medicine, primary care physicians already spend almost an entire DAY a week doing unreimbursed work between patient visits. I want the patient to do the “googling”, not me. I’ll do the interpreting, if asked, at the time of the next office visit.

The positive results of the first nationwide clinical study showing the benefits of an antiangiogenic agent in breast cancer therapy are reported in the Dec. 27 issue of the New England Journal of Medicine.

The study with Avastin showed the biggest improvement in metastatic breast cancer ever reported in a chemotherapy-based clinical trial. It nearly doubled the time between initiation of chemotherapy for metastatic disease and progression of the breast cancer tumors.

The study was coordinated by the Eastern Cooperative Oncology Group (ECOG) and Kathy Miller, M.D., associate professor of medicine and Sheila D. Ward Scholar at the Indiana University School of Medicine, is the lead author.

Dr. Miller said she found the results exciting because this was the first study to show that an antiangiogenic agent can delay progression of advanced breast cancer. The study looked at Taxol (paclitaxel), which is one of the standard agents for metastatic disease, with and without the addition of Avastin (bevacizumab).

“This study not only achieved the longest progression-free survival in advanced disease but the therapy achieved that improvement without adding to the day-to-day treatment burden and with only minor increases in toxicity,” said Dr. Miller.

The study enrolled 722 women with metastatic disease from the United States, Canada, Peru and South Africa. Patients were randomized to one of two arms of the phase III study Taxol alone or Taxol with Avastin. The patients, who joined the study from December 2001 through May 2004, represented a balance of age, disease-free interval, estrogen-positive receptors and sites of disease.

The results show that treatment with Taxol and Avastin increased the period patients went without progression of their disease from 5.9 months to 11.8 months.

“The next step is to move Avastin into the initial treatment of breast cancer in hopes that it will prevent recurrence in the first place,” said Dr. Miller.

Avastin is a human monoclonal antibody that acts to reduce the development of blood vessels that feed tumors. Cancer tumors need an increasing supply of blood to grow and the development of the blood vessels to supply the tumor is a process called angiogenesis. Avastin already has been approved by the Food and Drug Administration for treatment of colorectal and lung cancer.

The first clinical study with Avastin in humans was done in 1997 at Indiana University School of Medicine by George W. Sledge Jr., M.D., a pioneer in the field of antiangiogenic research. Dr. Sledge, a breast cancer specialist and the Ballve-Lantero Professor of Oncology, also conducted a 1998 Avastin study for breast cancer patients. Both early studies produced positive results.

Indiana University
http://www.indiana.edu

As reported recently in the journal Hepatology, WIN-R, a multicenter study of over 5,000 patients with hepatitis C virus (HCV) showed treatment with weight-based REBETOL® (ribavirin, USP) (RBV) in combination with pegylated interferon (PEG-IFN) alfa-2b achieved significantly higher rates of sustained virologic response (SVR) and lower relapse rates compared to combination therapy using a flat dose of RBV 800 mg/day. Superior response was found particularly in patients with the most difficult-to-treat form of the disease, genotype 1 HCV. Efficacy was consistent across all weight groups.

For patients infected with genotype 2 or 3, a 24 week course of treatment with flat dose RBV + PEG-IFN was as effective as the standard 48-week course, with better tolerability, and in the overall study population flat dosing of ribavirin was as effective as weight-based ribavirin. However, within the flat-dose cohort of patients with genotypes 2 and 3, sustained response rates showed a slight decline in the higher weight patients given flat-dosed ribavirin.

“These findings help define optimal therapy for U.S. hepatitis C patients,” says the study’s principal investigator, Dr. Ira M. Jacobson, the Vincent Astor Professor of Clinical Medicine at Weill Cornell Medical College and chief of the Division of Gastroenterology and Hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. “Our findings underscore that weight-based-dosed combination therapy is significantly more effective than the flat-dosed RBV regimen, especially in more difficult-to-treat patient groups, such as patients with genotype 1 and African-American patients. Patients being treated for hepatitis C should talk to their doctors to be sure they are receiving the most effective therapy.”

Reported in the same journal is a subanalysis of the WIN-R data that evaluates the efficacy of weight-based dosing among African-American participants with genotype 1 infection. Twice as many of these patients cleared the virus when treated with the weight-based RBV regimen vs. the flat dose (21% vs. 10%); a lower rate was shown in the general study population with genotype 1 HCV, 34% vs. 28.9%. (However, the fact that over 300 patients with an end of treatment response missed their 24-week, post-treatment follow-up appointment accounts for some treatment failures under a strict intent-to-treat analysis.)

“These results are particularly significant for African-Americans, a group with known lower rates of response to HCV therapy than reported in other ethnic groups. Weight-based dosing vs. flat dosing clearly showed the greatest therapeutic impact in this group,” says Dr. Jacobson.

“The study data strongly suggest adopting a 1400 mg/dose for patients who weigh more than 105 kg. In my opinion, the larger dose provides an opportunity for very heavy patients to have the same chance of cure as lighter patients without compromising safety,” says Dr. Jacobson.

Overall safety with weight-based dosing was similar to that of the flat 800 mg dose. There was no difference in the occurrence of serious adverse events in the entire group, as well as in the African-American group.

Researchers at NewYork-Presbyterian/Weill Cornell are at the forefront of developing more effective prescription therapy for patients with HCV genotype 1 and are testing many drugs in various stages of development.

Collaborating with the study’s principal investigator Dr. Jacobson was Dr. Robert S. Brown Jr., co-principal investigator of the study and associate professor of clinical medicine at Columbia University College of Physicians and Surgeons; and chief of clinical hepatology and medical director of the Center of Liver Disease and Transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center.

Dr. Jacobson is also medical director of the Center for the Study of Hepatitis C in New York City, a unique interdisciplinary Center established jointly by The Rockefeller University, New York-Presbyterian Hospital, and Weill Cornell Medical College. He serves as a consultant, investigator and speaker for Schering-Plough.

WIN-R Study

WIN-R (Weight-Based Dosing of PEG-INTRON and REBETOL) is a community-based access trial involving more than 5,000 patients at 225 centers across the U.S.

The uniquely large database of the WIN-R study allowed investigators to address other questions of interest, which have been presented at international meetings, including analyses of the response to HCV therapy based on age, baseline viral load, degree of liver fibrosis (scarring), and the study site at which the medication was delivered.

WIN-R is an investigator-initiated clinical study supported by Schering-Plough Corporation and monitored by Schering-Plough Research Institute as part of a post-marketing commitment to the U.S. Food and Drug Administration (FDA). PEG-INTRON and REBETOL are registered trademarks of Schering-Plough.

For over 10 years, Wafik S. El-Deiry, MD, PhD, Professor of Medicine, Genetics, and Pharmacology at the University of Pennsylvania School of Medicine, has been pursuing a cancer-targeting molecule called TRAIL and its molecular partners. TRAIL is normally produced by immune cells and curtails tumor spread by binding to a specialized receptor on a tumor’s surface.

“However, in cancer patients who often have suppressed immunity, and for reasons we still don’t understand, there isn’t enough TRAIL being produced, so tumors are not suppressed,” explains El-Deiry, who is also Co-Program Leader of the Radiation Biology Program for the Abramson Cancer Center at Penn.

Most recently, El-Deiry and colleagues demonstrated for the first time a link between TRAIL’s receptor and cancer susceptibility, as reported online December 13, 2007 in the Journal of Clinical Investigation in advance of the January 2008 print issue. Unexpectedly, they also found a connection via Trail between inflammation and cancer susceptibility.

Mice engineered without the TRAIL receptor on their cells versus healthy controls developed larger and more tumors in their livers and other organs after being challenged with a chemical carcinogen or radiation. The team also bred TRAIL receptor knock-out mice with mice genetically engineered to get B-cell lymphomas that metastasize to the liver. Their offspring displayed more liver tumors compared to controls. “This is the first direct in vivo evidence that loss of the tumor death-inducing TRAIL receptor confers cancer susceptibility,” says El-Deiry.

When intact, TRAIL and its receptor decrease the influx of inflammatory cells and molecules that can lead to cancer. New models of cancer have suggested a link between inflammation and cancer in the last five years, and El-Deiry is in the early stages of trying to understand this connection with respect to the TRAIL pathway.

For example, in this study, the mice without the TRAIL receptor that were irradiated developed chronic pneumonia, an inflammatory response, as well tumors, evidence pointing to the connection between cancer and inflammation via TRAIL. “One benefit of this work is that it provides a new and unanticipated model implicating a TRAIL pathway deficiency in the chronic toxicity of radiation therapy,” he notes. Inflammation is a common late and serious side-effect of radiation treatment in people.

El-Deiry and his team are now looking within tumor tissue for inflammatory molecules as clues to how cancer and inflammation are coupled. “Our work with TRAIL and its receptor in mouse models represents a new way to look at cancer susceptibility and its potential therapy in humans as well as new ways to decrease debilitating radiation side-effects experienced by cancer patients,” says El-Deiry.

Co-authors in addition to El-Deiry are Niklas Finnberg from Penn and Andres J.P. Klein-Szanto from Fox Chase Cancer Center, Philadelphia. This research was funded in part by the National Cancer Institute.

PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System.

Penn’s School of Medicine is currently ranked #3 in the nation in U.S. News & World Report’s survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation’s first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, comprised of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 300 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.

University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
http://www.med.upenn.edu

Northwest Biotherapeutics, Inc. (OTC Bulletin Board: NWBO) (AIM: NWBT; NWBS) (”NWBT”) announced that a Phase I/II clinical trial in at least 30 patients, using DCVax(R)-L for recurrent ovarian cancer, has begun at The University of Pennsylvania Center for Research on Early Detection and Cure of Ovarian Cancer and the Abramson Cancer Center. The first patients have been enrolled and have undergone initial treatment steps in preparation for receiving DCVax(R)-L. The trial involves two sequential studies, and comprises an innovative combination of multiple treatment modalities. DCVax(R)-L forms the cornerstone of the treatment regimen, and is complemented by administration of low doses of certain existing approved drugs to help improve the immune system environment, as well as by adoptive transfer of patients’ DCVax(R)-L primed T cells. The principal investigators for the trial are Dr. George Coukos and Dr. Sarah Kim, and the Penn Investigational New Drug (”IND”) sponsor is Dr. Carl June. The funding is being provided by the Ovarian Cancer Vaccine Initiative. (See below for more information about this Initiative.)

DCVax(R)-L is a personalized immunotherapy for cancer, which is made from a patient’s own dendritic cells (the master cells which initiate and manage the overall immune system response to a disease), and the “antigens” (biomarkers) from the patient’s own tumor tissue which has been surgically removed as part of the standard of care. Such immunotherapy is sometimes referred to as a “therapeutic vaccine,” as it is designed not to prevent cancer but to treat patients who already have cancer.

In the first study being conducted by NWBT and Penn, patients will first undergo standard surgery to reduce their tumor burden. Patients will then receive limited doses of two existing drugs to improve the immune system environment and modify the tumor vasculature. Cancer researchers have become increasingly focused on the role of tumor vasculature and the tumor microenvironment, as well as the possible role of a certain kind of cells called “regulatory T cells,” in causing a patient’s immune system to become unresponsive to the patient’s tumor, and on the potential importance of modifying these factors in order to achieve robust and durable immune responses against tumors.

Following the preparatory treatments, the patients in this ovarian cancer trial will receive a series of three immunizations with DCVax(R)-L, each two weeks apart, while continuing to receive the low doses of two drugs intended to keep the immune system and the tumor microenvironment in a beneficial condition.

The second study, which will be a follow-on to the first study but covered by a separate IND filing, will compare two treatment arms continuing further with the drug and DCVax(R)-L regimen, and adding the adoptive transfer of DCVax(R)-L primed, and expanded T cells.

By combining multiple diverse treatment modalities, structured around DCVax(R)-L as the cornerstone, this clinical trial is designed to implement evolving research findings on the complex interactions between tumors and the “host” tissues in patients, and evolving findings on the many facets of the immune system and what may be required for effective anti-tumor responses.

The trial is also designed to minimize any potential toxicity for patients. Clinical trial experience to date with DCVax(R)-L products in over 100 treatment cycles in brain cancer patients has shown no toxicity from the DCVax(R)-L treatment (no grade 3 or 4 adverse events). This multi-modal ovarian cancer trial has been designed to maintain this minimal-toxicity approach, by using only low doses of the two drugs complementing DCVax(R)-L for preparatory effects.

The first patients have been enrolled in the study by Dr. George Coukos. Dr. Coukos stated, “this is a very significant event for patients at the University of Pennsylvania and nationwide who are diagnosed with ovarian cancer. We are excited to work with Northwest Biotherapeutics on this cutting edge clinical trial, and to test the DCVax(R) platform on an additional cancer that carries a poor prognosis.”

Dr. Carl June, the Penn sponsor on the trial, stated, “the combination of DCVax(R)-L for ovarian cancer with adoptive immunotherapy using T cells primed by DCVax(R)-L is an innovative approach that deserves testing in clinical trials.”

“We are very pleased to add Ovarian cancer to the DCVax(R) platform, and to have Dr. George Coukos and Dr. Carl June lead this effort as the principal investigators for this clinical trial,” stated Alton Boynton, President and Chief Executive Officer of Northwest Biotherapeutics. “Drs. Coukos and June are world renowned experts in immunotherapy and in ovarian cancer. They are playing a major role in the pioneering of novel cancer treatment strategies — particularly by combining multiple different therapeutic approaches.”

Ovarian cancer is the fourth leading cause of cancer death among women in the U.S. Approximately 22,400 new cases were diagnosed in the U.S. in 2006, and about 15,300 deaths occurred. In the majority of ovarian cancer cases, the disease has already reached late stage, and spread beyond the ovaries, before it is detected and diagnosed. After initial surgical removal of tumors, and treatment with currently available drugs, the median time to disease recurrence is 18 to 20 months. Recurrent disease is considered incurable and usually results in death, even with aggressive chemotherapy treatments. Accordingly, there is a major unmet medical need for new and more effective treatments for ovarian cancer — especially recurrent ovarian cancer.

The DCVax(R) platform uses a patient’s own tumor, surgically removed as part of the standard of care, to prepare a mix of their personal cancer biomarkers. These personal cancer biomarkers are then loaded onto the patient’s own dendritic cells (the master cells responsible for starting and managing the body’s overall immune response), and injected back into the patient through a simple intra-dermal injection, similar to an insulin shot, at various intervals over a period of up to three years.