Personalized medicine, molecular targeting, advances in diagnostics such as CT/PET, mammograms, PSA tests, and a new blood test for lung cancer highlight recent progress in – and the future of –cancer diagnosis and treatment, say leaders of Florida Cancer Specialists.

“Forty years ago, there weren’t many options for cancer patients – only surgery, primitive chemotherapy, some radiation,” said Bill Harwin, MD, founder and president of Florida Cancer Specialists (FCS) & Research Institute. “Take kidney cancer, for example. Even 10 years ago, there were only one or two options for treatment. Now there are at least five or six new therapies that have extended the lives of these patients in some cases, a decade or more.”

The oncology community is just beginning to understand the mechanisms and pathways of cancer, and uses targeted therapies on a molecular level to prevent them from growing, Harwin pointed out.

“We’ve found ‘cures’ for some types of cancer, such as a pill that’s now given for chronic myelogenous leukemia (CML),” said Harwin. “Also, many breast cancers if caught early are curable. Even if a cancer isn’t curable, it’s manageable in many cases. Most forms of cancer are becoming more like chronic diseases to manage, such as high blood pressure or diabetes.”

Not only is the quantity of life with cancer being extended, but also the quality of life has improved, noted Harwin.

“There are many secondary medicines that prevent nausea, and even hair loss from chemotherapy,” he said. “Most cancer patients undergoing chemotherapy don’t get sick, and they lead relatively normal lives while in active treatment. It’s also rare for a cancer patient to be hospitalized because of the effects of chemotherapy. Twenty years ago, most patients had to be hospitalized to even receive chemotherapy because it was so toxic.”

Researchers and scientists are looking at the cellular and molecular levels to find more cures, identifying markers such as certain proteins that they can target, eliminate, and thereby destroy the cancer cells, said Harwin.

“We’re able to provide treatments to cancer patients that were only dreamed about 10 years ago,” he said. “And, most doctors will tell you that we’re just now beginning to scratch the surface of what will be available in the next 10 years.”

That’s why Harwin made certain to build FCS deliberately. It’s now the largest privately-owned oncology/hematology practice in the United States, with 120 doctors, 60 nurse practitioners, and a payroll of 1,400 employees at 52 sites within the private network. FCS collaborates heavily with the Sarah Cannon Research Institute (SCRI), one of the nation’s largest clinical research programs. As a result, FCS offers patients access to more national clinical trials than any private oncology practice in Florida.

“We have the newest and most promising therapy options available in almost every nature of cancer, and we have early stage Phase 1 trials available for almost any cancer,” said Harwin. “We’re very committed to research and want to offer at least one research trial to every patient who might be eligible for such trials.”

Roughly 5 to 10 percent of FCS patients are involved in clinical trials, “an outstanding number relative to the rest of the nation,” he noted.

Linchpin Development

Lowell L. Hart, MD, was one of Harwin’s early leadership recruits. The two had met at the University of Miami. Hart was a Duke professor when Harwin asked him to join the private practice. He now serves as scientific director of clinical research and director of the drug development program, in which FCS typically has 40 ongoing Phase 2 and 3 trials, and roughly 10 active Phase 1 trials.

“So much progress has been made in cancer treatment,” said Hart. “I’m particularly interested in a drug for breast cancer, TDM1, for which we’re doing two trials. It’s a combination of an antibody that’s been out for a number of years called Herceptin with one molecule of a very active chemotherapy drug called Maytansine. Maytansine was studied many years ago, but given intravenously, it was too toxic. The idea then became to target this molecule with Herceptin so it doesn’t go through the rest of the body. It targets breast cancer cells and zaps them with the antibodies.”

Only one of four breast cancer patients will have HER2 positive – mostly younger women who haven’t endured childbirth – yet it’s a particularly aggressive type of cancer, Hart said.

“That number still represents a fairly significant group of women,” he said. “One study is a final randomized trial that will hopefully allow the drug to gain FDA approval within the next year or two. Two of three women receive the drug; one of three patients will receive chemotherapy of their doctor’s choice, plus Herceptin. Our hypothesis is that the drug will work better by itself.”

Also, an international study for breast cancer patients with abnormal liver function is of significance, said Hart. 

“Because many women with this type of breast cancer will get involvement of the liver, unfortunately, from the cancer and their liver function tests will become abnormal, it’s difficult to measure the right dose of various chemotherapy drugs,” he said, noting that by comparison, it’s a much smaller study. “Much of the chemotherapy we administer is cleared out of the body through the liver, so if the liver isn’t working up to par, it’s hard to know the right dosage. We’re looking at that subset specifically to see if we can give the drug safely. This international study is also being done with some doctors in Nashville, Europe and a few other places.”

Hart likes other new drug therapies in cancer treatment such as Provenge, the very first of a new class of drugs called immunotherapies. Used in the treatment of Stage 4 metatastic prostate cancer, Provenge uses a patient’s own white blood cells to attack cancer cells.

“In addition to our clinical trials, there’s also a tremendous need for more and better various cancer screening studies,” he said. “Because screening trials have to be very large studies, they can only be run by the government or through a cooperative involving many hundreds of doctors,” said Hart. “Getting government funding for those sorts of studies is difficult in very tight economic times. The pharmaceutical and biotechnology companies are busy developing drugs and compounds that will make their way to market. Unless you can find private funding for these very expensive studies, it’s difficult to do because, aside from mammography and colonoscopy screening that were introduced 20 years ago, screening studies are always very controversial. I honestly think that what’s going to come next is blood test screening for cancers with fragments of tumor DNA and strictly tumor cells. That technology isn’t far off. And soon, I believe we’ll be able to screen effectively with blood tests for cancer. Even PSA screening is extremely controversial for prostate cancer. So is CA125, the blood test for ovarian cancer. Within five or 10 years, my prediction is that we’ll have better, easier, and safer screening tests through looking at proteins in the blood and little fragments of tumor DNA in the blood.”

Research Depth

Rob Whorf, MD, director of research operations for FCS, acknowledged it’s highly unusual to have such a high level of research in a community-based oncology practice.

“We have one of the few community-based programs in the country,” he said. “In most instances, you’ll only find Phase 1 trials and drug development at large, academic medical centers.”

Evidence-based guidelines for the National Comprehensive Cancer Network (NCCN), an alliance of 21 of the world's leading cancer centers, recommend clinical trials as the first option for patients, noted Whorf.

“The only way cancer therapies will improve is through further research,” he said. “Due to the close scrutiny of clinical trials and the rigorous review process they have to go through, it’s felt that being on a clinical trial assures one of receiving at least the standard of care or possibly the future’s new standard of care.”

FCS uses the “thought-leader” model for their Scientific Research Board, with each cancer subtype overseen by an oncologist dedicated to that specialized area of knowledge.

“This helps ensure high quality oversight and advances the knowledge-base for the entire practice,” he said.

FCS is fast becoming recognized around the globe for its expansive and comprehensive high-tech scientific research program, noted Whorf.

“The goal is to accomplish more while continuously striving to achieve the highest quality measures possible,” he said.

Of the most important breakthroughs in cancer treatment, and the most promising therapies on the horizon, two are truly exciting, noted Whorf.

“The new ‘platform’ of linking toxic chemotherapy directly to a target-specific antibody that delivers chemotherapy only to the target of interest – a ‘smart bomb,’ if you will,” he said. “The other identifies new signal transduction pathways in cells that are aberrant in cancer cells and targets those pathways specifically with small molecule inhibitors.  Someday, we’ll be able to identify the specific series of mutations in a person’s individual cancer and assemble a cocktail of well-tolerated oral inhibitors that work in concert for that person’s unique cancer.”

Expanding Roots

Harwin made certain to carefully hand-pick his leadership team with specialists like Hart, Whorf and Mark Rubin, MD.

In the early 1990s while working in a lab at Memorial Sloan Kettering, Rubin collaborated with legendary research pioneer John Mendelson, MD, former CEO of MD Anderson Cancer Center in Houston, to develop the drug C225, which would later become the drug Erbitux, an EGRF (epidermal growth factor receptor) inhibitor considered a “breakthrough” treatment. One of the very first targeted therapies, Erbitux binds to growth factor receptors and turns off the signal for the cell to divide. Their work represented a dramatic breakthrough in the way researchers thought about the treatment of cancer. Rubin joined FCS in the mid-1990s.

In 1998, Shannon Kellum, a young woman with metastatic colon cancer, became his patient. When all standard treatment failed, and because of the promise it had shown in the laboratory, Rubin suggested trying C225, which had not yet been approved by the FDA. He received permission from the drug company to use C225 with his patient for end-stage compassionate care. The drug was being developed for use in head and neck cancer and had never before been considered for the treatment of colon cancer. Because of Rubin’s innovative thinking, his patient survived four more years with a good quality of life.

“Very much the mood at that time (of the development of C225) was that we were on the forefront of a different way of understanding cancer,” said Rubin. “Previously, it had been more of an empiric approach where we would ‘poison’ the cancer cells and hope for the best, so there was a lot of trial and error. Dr. Mendelsohn was one of the first to understand that there were these growth pathways that were critical to cancer cells growing and dividing.  He knew that if those pathways could be targeted, it could potentially offer a new way to tackle cancer without affecting the good cells.  So that is what we were trying to do.”

As a researcher, Rubin learned to depart from oncological orthodoxy to pursue new ways of fighting cancer.

“We should be encouraging innovative thinking, but unfortunately, our society has demanded so much regimentation that often we regiment away innovation,” he explained. “Dr. Mendelsohn encouraged me to think beyond what you’re taught and to imagine the impossible. If you look at the history of medicine, many of the breakthroughs in every field weren’t based on the results of a huge study, but rather someone had an intuitive thought about how to solve a particular problem and that kind of innovative thinking then led to a huge study. If we stifle that out-of-the box, intuitive approach, we’ll restrain medical progress.”

Rubin likes the concept that as a practice, FCS isn’t leaving research to academic medical centers.

“We now have two drug development units that are aggressively pursuing new therapies and new ways of fighting cancer,” he said.

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 Year 1: FCS’s DDU in Sarasota Exceeding Expectations (455)

SARASOTA –In a rare move for a community-based practice, Florida Cancer Specialists (FCS) opened a second Drug Development Unit (DDU) last July to conduct Phase 1 or 2 clinical trials with complex laboratory processes.  

The Sarasota DDU joins FCS’s established Fort Myers DDU.

“FCS is one of the very few community practices in the world that’s able to perform Phase I clinical trials,” said Manish Patel, MD, manager of the Phase I clinical trials in Sarasota, who also helps direct FCS’s entire Phase I clinical trial program. “Patients who seek these trials often have to travel great distances, as they are typically performed at large academic centers. The convenience of our patients is one of the primary reasons FCS decided to open a second DDU in Sarasota.”

Patel, who only sees patients in Phase 1 clinical trials that have failed standard treatment or lack alternative therapies, works closely with the Sarah Cannon Research Institute (SCRI) on FCS’s sophisticated clinical trials program at the Sarasota Cattlemen’s office, also serving as the associate director of drug development for SCRI, one of the nation’s largest community-based clinical trial organizations.

“All of the cancer patients that I treat are on one of our clinical trials and are referred from our sites in Florida,” he said. “Fortunately, I also have the opportunity at SCRI to help plan these clinical trials at an early stage and bring them to our FCS patients.”

Phase I clinical trials typically consist of drugs that are at an earlier stage of development where establishing a tolerable dose is often the primary goal. However, Phase I clinical trials are also often performed after successful Phase II and III trials have been completed to further examine drug formulation, dose, cardiac safety, and drug-drug interactions. Because of their complex design, Phase I trials can only be conducted at locations that have appropriate resources, infrastructure, and expertise. Therefore, these trials can often provide an innovative treatment option for patients that would otherwise not be available, Patel explained.

“Every treatment that’s available to us as standard of care is a result of success seen with the drugs on prior clinical trials,” he said. “After proving safety, tolerability, and efficacy through the various phases of clinical research, these study drugs are eventually approved by the FDA and can be used for our patients. This process is heavily reliant on the results of Phase I clinical trials.”

Clinical research has become more sophisticated as therapy is better targeted and formulated with more innovative technology. Specific pathways that are known to be present in cancer development are now being specifically targeted for treatment, said Patel. 

“Oncology has made tremendous strides in identifying targets for treatment at a molecular level,” he said. 

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William N. Harwin, MD

President, Florida Cancer Specialists & Research Institute

After earning an undergraduate degree from Oberlin College in Ohio and graduating from the Baylor College of Medicine in Houston, Bill Harwin, MD, completed his internship and residency in internal medicine, followed by a fellowship in hematology and medical oncology at the University of Miami. Board-certified in internal medicine, medical oncology, and hematology, Harwin formerly presided over FLASCO (Florida Society of Clinical Oncology). For 26 years, Harwin has deftly juggled a thriving medical practice with investigative clinical research. In 1997, he performed the first peripheral stem cell transplant in Lee County for a woman with breast cancer. A noted lecturer with published articles in leading medical journals, he is consistently named a best doctor in regional and national professional recognition programs.

Lowell L. Hart, MD

Scientific Director of Clinical Research

Director, Drug Development Program
Lowell Hart, MD, oversees the extensive clinical trial and research program at FCS. After earning an undergraduate degree from Columbia University and his medical degree from State University of New York (SUNY), he completed his internship and residency at the University of Miami Hospitals. He then completed a fellowship in hematology and oncology with Duke University Medical Center, later serving as an attending physician in Duke’s Breast Oncology Clinic. Hart was among the first oncologists to join FCS in 1989. In 2003, he was named FCS research director. His clinical trial investigation work and research results have been extensively published. In 2010 and 2011, Hart was a guest participant at the International Breast Cancer Conference in Paris.

Manish R. Patel, MD

Associate Director of Research and of the Drug Development Unit (DDU) in Sarasota

Board certified in internal medicine, medical oncology and hematology, Manish Patel, MD, sees patients in the FCS Sarasota office and helps manage the DDU in Sarasota. After graduating from the University of Florida, he earned a medical degree from the University of Miami, followed by a residency at Vanderbilt University and a fellowship in the H. Lee Moffitt Cancer Center in Tampa via the University of South Florida. A highly sought-after recruit, he joined FCS when the Sarasota DDU opened last July.

Mark S. Rubin, MD

Director, FCS Executive Board

Board certified in internal medicine, medical oncology and hematology, Mark Rubin, MD, sees patients in the FCS Bonita Springs office. Recognized early on as a brilliant researcher and practitioner, the Harvard University graduate earned a medical degree from Columbia University, and then completed an internship and residency at UCLA Medical Center, followed by a fellowship in hematology and oncology at Memorial Sloan-Kettering Cancer Center. 

Robert C. Whorf, MD

Director of Research Operations
Rob Whorf, MD, manages the development and implementation of new methods for expanding research protocols and the daily operations of the research department at FCS. In addition to increasing participation in clinical trials, Whorf also oversees the Drug Development Unit (DDU) in Fort Myers and Sarasota. After completing graduate studies in neuroscience at Harvard University, Whorf earned a medical degree from the University of Rochester, where he remained for his internship and medical residency. He then completed a fellowship in medical oncology at Yale University School of Medicine. Whorf joined FCS in 2004, where he has been involved in leadership roles for some 60 clinical research trials and has published in such prestigious periodicals as the Journal of Clinical Oncology and the Journal of Neurobiology. U.S. News and World Report named him one of the Top Doctors in the United States in 2011.

SIDEBAR:

Personal Best

Clinical trials to advance breast cancer treatment are near to the heart of Florida Cancer Specialists & Research Institute founder and CEO Bill Harwin, MD. His wife, Marilyn, the mother of their four children, was diagnosed with Stage 1 breast cancer at the age of 37. After five years in recession, the cancer reemerged and aggressively spread. She died nearly six years ago.

To honor her memory, Harwin, a biking enthusiast and an avid runner who has completed marathons in New York City, Chicago, and Honolulu, participates in the Pan Mass Challenge, a nearly 200-mile annual biking event that raises money for breast cancer research at Dana Farber Cancer Institute in Boston.

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