The 40-Year War

It was 40 years ago in January that Richard Nixon, still grappling with the Vietnam War and not yet overwhelmed by scandal, stood before Congress to deliver the State of the Union address and declared a bold new goal for the nation.

The federal government would launch an “intensive campaign to find a cure for cancer,” devoting as much attention to the disease as it had to splitting the atom and reaching the moon, Nixon said.

Although he did not say the words, Nixon became the man who declared “war on cancer.” By year’s end, he had signed the National Cancer Act of 1971, making “the conquest of cancer a national crusade.” The act set aside $100 million to create cancer centers and fund new research.

Today, the National Cancer Institute (NCI) spends more than $5 billion a year. Opinions abound about how the war on cancer has been waged and what has been “won.” While cancer is no longer the death sentence it was in the 1970s, the American Cancer Society predicts that more than 1.5 million people in the United States will be newly diagnosed with the disease this year.

“It is not unreasonable to state that we are actually at the beginning of the war on cancer,’ since we now have for the first time a genuine understanding of the fundamental molecular pathways that are the main drivers in the progression of malignant disease,” said Maurie Markman, MD, vice president of Patient Oncology Services and national director for Medical Oncology at the Cancer Treatment Centers of America, Philadelphia, Pennsylvania, and editor-in-chief of Oncology Net Guide.

“Unfortunately, we are also now very aware of the true complexity of cancer, and the fact it is highly unlikely a ‘magic bullet’ will be discovered that will cure all, or most malignant conditions,” he said. “Further, evidence suggests that a more successful strategy will be to consider many advanced malignant diseases to be serious chronic illnesses, where ‘cure’ is an unrealistic goal but where extended control, possibly measured in ‘years,’ is a legitimate possibility.”

As in any war, the perspective of those on the battlefield often depends on their vantage point. Oncology Net Guide asked researchers and clinicians to mark some of the milestones in technology and biomedical research that have occurred during the war on cancer and discuss how these changes have affected their practices.

Robotic Tools Revolutionize Prostate Care

Ihor Sawczuk, MD, is co-chair of Urologic Oncology at the John Theurer Cancer Center, Hackensack, New Jersey. He measures the manner in which technology has revolutionized care by changes in the way oncologists recognize and treat prostate cancer. Physicians have long known the anatomy of the prostate; the da Vinci Robotic Surgery System, with 10 times magnification and high-definition imaging, offers new and expanded views.

“Those areas that we knew about, now we saw them in a way that was never possible,” Sawczuk said. “And when you looked at it you said, ‘Okay, let me rethink those areas and how I can improve on what I’ve been doing surgically. Improve my techniques. Make them finer.’ Doing so improves the quality of life for the patient, and the outcomes.”

The benefits of robotic technology are numerous, Sawczuk said. There is very little blood loss, so transfusion rates have decreased significantly. “We probably transfuse one to two percent of patients who undergo radical prostectomy with the robotic technique, compared with a 30 to 40 percent transfusion rate with open procedures.” In addition, pain control is better due to the smaller incisions, and patients’ return to normal work functions is more rapid due to the laparoscopic technique. With quality-of- life issues such as incontinence, the return to normal control of urination appears to be a faster process, according to Sawczuk.

The growth and acceptance of the da Vinci system has been rapid as well. In 2005, the national usage rate was approximately 20 percent. Today, it ranges from 70 to 75 percent. The rate of utilization throughout the John Theurer Cancer Center is about 98 percent, said Sawczuk, who first adopted robotics in 2004.

“I found that the equipment allowed me to utilize my normal hand functions; I just had to learn a new piece of technology,” he said. “And that was the beauty of the da Vinci robot. It allowed six-degree freedoms of hand rotations. It didn’t limit you to straight laparoscopy, which is like operating with chopsticks. There was natural progression to enter that machine.”

What’s next? Sawczuk said he envisions operating rooms using virtual technology, where doctors may not have to actually sit at a machine. Instead, the machine will be all around them. “Like in the movies,” he said. “You’ll be standing there, moving your head, moving your hands, and things will respond to you. I can certainly see that in my lifetime.”

Pharmacy Management Grows in Importance

The history of cancer treatment started with surgery, a modality that continues to play an important role today. What has evolved considerably over the years, however, is the role of medical oncology—specifically, pharmaceuticals. From the early days of extremely toxic treatments such as mustard gas to today’s oral oncology drugs, therapeutic regimens have become much more complex. As such, the role of pharmacy management has taken on added importance.

Milayna Subar, MD, vice president and national practice leader for Medco Oncology Therapeutic Resource Center, Whitestown, Indiana, said the interaction of drugs cancer patients take for other medical reasons requires increased vigilance. In January, pharmacy benefits manager Medco Health Solutions Inc, Franklin Lakes, New Jersey, launched the oncology center to improve monitoring of drug interactions, saying cancer patients take on average 10 different oral medications.

Pharmacists at the Oncology Resource Center review prescriptions with an eye to the dose, the disease, and the combination with other therapies patients may be receiving, Subar said.

For example, Subar noted that women taking tamoxifen for breast cancer might also be using an antidepressant that can interact with and limit the effectiveness of the anti-cancer drug. She also said cancer patients, particularly older people, are being treated for other conditions at the time of their cancer diagnosis.

“The older population has other conditions, like hypertension, diabetes, and heart disease,” said Subar. “We need to be aware of the multiple drugs that patients are taking.”

Subar said prior authorization procedures go beyond cost considerations. “Cost is important, but it’s important combined with safety and managing drug dispensing,” she said. “If there’s a genetic mutation in the cancer, and that mutation is known to make this particular kind of cancer resistant to a specific drug, then giving that drug is a waste. Yes, a waste in terms of money, but it’s also a waste in terms of the patient’s time. And a cancer patient who is getting a drug that we can predict will not work will have that cancer progress.”

Subar said that nutrition care for cancer patients is another area of growing interest. Medco subsidiary TherapEase Cuisine, Greenfield, Wisconsin, offers clinically developed meal programs. There are foods that reduce the impact of adverse effects, foods that worsen adverse effects, and some foods that help cancer patients maintain weight. “We’re really making inroads into the nutrition area,” Subar said. “We’re really trying to take a 360-degree view of the patient.”

Success Stories in Treating Pediatric Cancers

When the war on cancer was launched, the NCI recognized that cancer was less prevalent among children than adults. In contrast to adult cancer rates, the incidence of childhood cancers remains small—less than 1% of all new cancer cases diagnosed this year are expected to be in children ≥14.2 For progress to be made in the area of pediatric cancer, considerable coordination and cooperation between centers would be required.

David Poplack, MD, director of the Texas Children’s Cancer Center, Houston, confirms that need for cooperation, pointing out that, “We are the largest children’s cancer center in the US, but even we can’t do many studies and come to any clinical significance unless we do them cooperatively.” That recognition, he said, has led to the dramatic improvements that have been seen in childhood cancers.

For starters, almost three-quarters of the pediatric cancer patient population participate in clinical trials. In contrast, only 3% to 5% of adult cancer patients enter clinical trials. Although the number of adults enrolled in trials far exceeds the number of children involved in studies, Poplack said “pediatric oncology is the subspecialty of medicine that is most closely associated with research.”

In the late 1940s, when the first form of chemotherapy was used to treat children with cancer, the long-term survival rate for children who had cancers removed surgically was approximately 5%. Today, Poplack said, between 75% to 80% are being cured. That means they have completed therapy, have been off treatment for 2 years, and have become long-term survivors.

“The improvement in treatment for ALL (acute lymphoblastic leukemia), the most common form of childhood leukemia, has dramatically improved, such that we’re now curing approximately 80% of children with ALL,” Poplack said. “When this all began, the figures were down in the 20% range. And if you look at the clinical trials that have demonstrated progress, and you add up the number of patients, all of these improvements occurred through the treatment of approximately 13,000 patients who entered these various clinical trials over those years.”

The challenge going forward, said Poplack, is handling the impact of therapies routinely given to children 30 years ago that have since been associated with adverse late effects in about 75% of patients. In as many of 25% of those patients, the effects are potentially life threatening. Working with the Children’s Oncology Group, a worldwide clinical trial cooperative group, the cancer center has developed the Passport for Care—an Internet-based resource that individualizes the follow-up care for long-term survivors of childhood cancer.

“Individuals are able to see what they’re at risk for, and it gives them information as to how and when they need to be screened,” Poplack said. “It will revolutionize the way long-term survivors are followed. And we will apply this tool, eventually, to survivors of adult cancer.”

Advances in Radiotherapy Generate Optimism

Nancy Mendenhall, MD, is professor and associate chair of the Department of Radiation Oncology at the University of Florida College of Medicine, Gainesville. She also serves as the medical director of the UF Proton Therapy Institute, Jacksonville, Florida. As such, she’s well versed on the progress in radiation oncology.

She recalls the large clinical trials of decades past where thousands of breast cancer patients were randomized to receive, or not receive, radiation. Such trials showed a reduction in the incidence of local recurrence, but they did not show a survival advantage. “As radiation oncologists, we did not have the diagnostic tools that we needed to understand where all the local and regional disease was, and how to target it,” Mendenhall said. The availability of computed tomography scans circa 1990 provided a major step forward.

The 3-dimensional imaging enabled oncologists to better target the areas at risk. But that, said Mendenhall, was only half the equation.

“Surgery and radiation are not only ablative, they’re also nonspecific,” she said. “That means you have to contend with damage you may be causing to important normal tissues when you use either surgery or radiation. And so the key to achieving the highest therapeutic ratio with radiation is dose distribution—getting the radiation dose to the target, and minimizing the radiation dose to the normal tissue.”

Today, the gold standard in that regard is Intensity Modulated Radiation Therapy, where the highest concentration of radiation conforms much more locally to the shape of the tumor. “That’s a huge distance to have traveled from 1980 to 2005 in terms of dose distribution,” Mendenhall said. However, low doses of radiation still affect areas surrounding the tumor, and “even those low doses cause problems, such as the loss of IQ” in brain tumor patients.

Mendenhall believes the advent of proton therapy is the next step forward in advancing dose distribution. “No longer are we using photons, which are x-rays or gamma rays. We’re now using particles, and particles don’t go all the way through the patient. With protons, they stop on the target so you’re eliminating the dose to the normal tissues. Now what we need is a little bit of time, and some clinical trials, to document the improvement and outcomes that we’re going to see. And we will see them.”

Tiny Particles Might Yield Big Results

At the MD Anderson Cancer Center, Houston, Texas, research is continuing into noninvasive cancer treatments through nanobiomedicine. Steven A. Curley, MD, professor of surgery, chief of Gastrointestinal Tumor Surgery, and program director of Multidisciplinary Gastrointestinal Cancer Care at MD Anderson, also is the lead investigator for the Kanzius Non-Invasive RF Cancer Treatment program. He believes that nanobiomedicine holds the potential to realize major advances in cancer treatment during the next 5 to 10 years.

Kanzius scientists, supported by the Kanzius Cancer Research Foundation, Erie Pennsylvania, have been introducing microscopic metals known as nanoparticles into a cancer patient’s bloodstream. These particles attach themselves to cancer cells, and Kanzius’ noninvasive treatment then generates enough heat to destroy the cancer with no adverse effects. Researchers conducting tests with Kanzius equipment have been able to kill 100 percent of the cancer cells in small, live animals in vitro without harming nearby healthy cells. Work has been conducted on several cancer types, including pancreas, liver, colorectal, breast, and prostate.

Now Curley is excited about the next steps.

“The engineering group I’m working with has completed the design and is starting to build a device that’s large enough to treat humans,” he said. “We’ll need to do some large animal testing first, but with that I can then go to the FDA to say this is the model we’re going to use. My hope is to be in human clinical trials in two to three years.”

That may sound like a long time, but not when compared with a war that is nearly 40 years old. “The way I look at these treatments is we’re trying to convert cancer to a more chronic disease,” said Curley. “And in many cancers we’re being successful. So while we may not cure an individual, while they may not ever become cancer free, if they can live with the cancer for prolonged periods and have a good quality of life, then that is a very sane and reasonable goal.”

Andrew Pecora, MD, FACP, chairman and executive administrative director of the John Theurer Cancer Center, also is heartened by the progress that has been made against cancer.

“If you had chronic myelogenous leukemia 15 to 20 years ago, unless you had a bone marrow transplant, you were going to die within three to four years,” Pecora said. “Now you take a pill once a day and your leukemia goes away. You may not be cured, but your leukemia goes away and stays in remission

“Our outcomes are much better,” he said. “I came here in 1989, and the average life expectancy of a woman with breast cancer that spreads to other parts of the body was measured in a couple of years. Now it’s measured in decades. It’s so dramatically different. Not for everybody, but for many.”