A Man of Many Battles: Genitourinary Expert Spurs Advances Amid Challenges

Photo courtesy of Comprehensive Cancer Centers of Nevada

Nicholas J. Vogelzang, MD

Nicholas Vogelzang knows what it’s like to start over.

During his career as a medical oncologist and researcher, the genitourinary expert has tackled several ventures, including a bold departure from a long-term university post to join a startup cancer center, as well as his current roles at Comprehensive Cancer Centers of Nevada (CCCN), where he treats patients, and US Oncology in Houston, Texas, where he helps lead clinical research.

In his personal life, the 62-year-old has weathered a cardiac bypass, divorce, the loss of a child, a battle with Hodgkin disease, and his wife’s recent battle with sarcoma.

So, when it comes to helping patients fight for another chance at life, Vogelzang is prepared.

“Cancer can be treated; it can be maintained and controlled,” the doctor said. “That’s what I tell patients: ‘If you want to fight this cancer, I’ll fight alongside you.’”

Vogelzang helps about 100 patients each week to wage that battle. Most of those he treats have prostate cancer, and the others have kidney, bladder, or testicular cancers—or mesothelioma, an area of expertise left over from Vogelzang’s early years as a lung cancer specialist. It’s typical for the doctor’s patients to hail from as far away as southwestern California, Washington, Idaho, New Mexico, and Utah.

Vogelzang touches the lives of additional cancer patients through his involvement in the design of clinical trials, and as part of the steering committees for large pharmaceutical- sponsored phase III trials. He serves as vice chair of the SWOG (formerly the Southwest Oncology Group) Genitourinary Committee, and serves on US Oncology’s Research Executive Committee, as co-chair of its Genitourinary Committee, and as chair of its Developmental Therapeutic Committee. Vogelzang also helps hatch clinical trial design ideas as a member of 10 pharmaceutical advisory boards.

Through those efforts, the award-winning doctor and researcher, who also lectures around the world and finds time for membership in a dizzying number of medical advisory committees, has changed the course of cancer treatment by helping to develop therapies for prostate cancer, kidney cancer, bladder cancer, testicular cancer, and mesothelioma.

Research Achievements Mount

During two decades at the University of Chicago, Vogelzang conducted studies in mesothelioma, culminating in the February 2004 approval of the chemotherapy agent pemetrexed disodium (Alimta) (J Clin Oncol. 2003; 21(14):2636-44).

The drug was approved in combination with cisplatin for patients with malignant pleural mesothelioma who have unresectable disease or are not otherwise candidates for curative surgery. Vogelzang’s multicenter, randomized trial that led to the approval demonstrated that pemetrexed and cisplatin added a statistically significant survival advantage for those patients as compared with cisplatin alone. “Still, nearly nine years later, it remains the standard of care,” Vogelzang said.

Vogelzang is proud to have been on the advisory board for, and a contributor to, studies that led to the April 2011 approval of the hormonal treatment abiraterone (Zytiga); the drug, given in combination with prednisone, has changed the treatment paradigm for patients with metastatic castration-resistant prostate cancer who have previously taken docetaxel.

In addition, the doctor’s research into the antineoplastic drug mitoxantrone helped pave the way for its 1996 FDA approval as the first nonhormonal therapy for the treatment of prostate cancer. While the results weren’t earth-shaking for patients, Vogelzang said, they made a big difference in the path of prostate cancer research.

“Mitoxantrone wasn’t very effective, but it did allow us to then compare that drug to docetaxel,” leading to the standardchanging establishment of the taxane as a treatment for prostate cancer, he said.

Vogelzang, who enrolled more patients in clinical trials last year than any other doctor at US Oncology, has also helped to launch three patient support groups: Us TOO, for prostate cancer patients; the Kidney Cancer Association; and the Mesothelioma Applied Research Foundation.

Nicholas J. Vogelzang, MD . . .

• Is devoted to his five children and his seven grandchildren, who range in age from 1 to 10.
• Is “addicted” to reading, particularly autobiographies and histories such as Unbroken: A World War II Story of Survival, Resilience, and Redemption, by Laura Hillenbrand. “When I have the chance, I’ll read all night,” he said. “I have to be careful about how many books I read, so I don’t get too tied up and get behind on my real work.”
• Enjoys riding his road bike between 60 and 100 miles a week in the Nevada desert and mountains.
• Is of Dutch heritage, and grew up “attending tulip festivals and wearing a little Dutch hat and little wooden shoes.”
• Held a series of less-than-ideal jobs during high school and college, including cleaning out dry-cleaning vats, scrubbing toilets and floors, and working at a plant testing plaster mixed with asbestos. As someone who now treats mesothelioma, frequently caused by asbestos exposure, Vogelzang sees “the irony” in that experience. “At the time, I had no idea” that asbestos was dangerous, he said. “The plant manager was a member of our church, and I was happy to have a job.”
• Is a survivor of Hodgkin disease.
• Has served on numerous committees of the American Society of Clinical Oncology (ASCO), and won the organization’s Statesman Award in June 2007.
• Firmly supports ASCO’s August clinical provision report published in the Journal of Clinical Oncology, which says that PSA screening should be strongly considered for certain groups at high risk for prostate cancer. “It’s more nuanced than the bludgeoning approach of the US Preventive Services Task Force, which is ‘don’t screen.’ That approach is not smart, because medicine is not black and white,” Vogelzang said. “For a patient truly at risk because of genetics or race, the PSA test should be ordered so the patient can make a decision for or against active treatment. The problem to avoid is being overly aggressive with our treatments, not our screenings.”
• Sees immunotherapy as well as the genetic profiling of cancers as the most important frontiers to be tackled by today’s cancer researchers.
• Is grateful to his wife, children, and grandchildren for “not giving up on me in spite of the long hours I work,” and to “the patients, who are enormously stimulating, kind, and thoughtful. Their courage encourages me every day.

“I put in a lot of time,” he said, “but patients needed to be empowered. They help raise money and give emotional, physical, and financial support to other patients. They’re very important groups.”

Eureka Moments Drove Career

It was his awe over advances in the treatment of testicular cancer that lured Vogelzang into genitourinary oncology.

Having graduated from Trinity Christian College in Palos Heights, Illinois, and having earned his medical degree from the University of Illinois Abraham Lincoln School of Medicine after being accepted early as a James Scholar, Vogelzang developed a focus on lung cancer during his residency at Rush Presbyterian St. Luke’s Medical Center, in Chicago. In 1978, he left for the University of Minnesota to pursue a fellowship in that field.

“But, in Minnesota, there are a large number of Norwegians, Swedes, Danes, and Germans who have a high rate of testicular cancer,” Vogelzang said. “Around that time, platinum came into use, and we were able to cure young men who otherwise would not have been curable. It was an indelible experience for me.”

When Vogelzang was recruited in 1982 to the University of Chicago, a lung cancer specialist was already on board. The chief of Hematology/Oncology who hired Vogelzang, Harvey M. Golomb, MD, told him, “You’re going to do testicular, prostate, kidney, and bladder cancer,” Vogelzang recalled. “It was like being assigned by the general to do something, and I did it. I’ve written 400 to 500 papers in the field now.”

During 21 years with the university, Vogelzang worked closely with Mark J. Ratain, MD, on phase I trials and with Richard L. Schilsky, MD, within Cancer and Leukemia Group B (CALGB), eventually succeeding Schilsky as director of the university’s cancer center. Vogelzang was also selected to become the first Fred C. Buffett Professor of Medicine and Chair in Genitourinary Oncology. The endowed chair was inspired by Vogelzang’s treatment of one of his patients, and was among the doctor’s greatest honors.

“I took care of Fred Buffett, the nephew of [businessman and investor] Warren Buffet,” Vogelzang recalled. “He was a wonderful guy, a solid human being. Fred’s wife and daughter, through their Rebecca Susan Buffett Foundation, were extremely generous with the university, and donated $2 million in Fred’s name to endow a chair.” That chair is now held by Walter M. Stadler, MD, Vogelzang’s longstanding colleague in genitourinary oncology research.

During his years in Chicago, Vogelzang experienced a couple of “eureka” moments, the kind that continue to fuel his excitement about his field.

One occurred in the early days of testing sorafenib in patients with advanced renal cell carcinoma (RCC). The drug was approved for use in the disease in late 2005, and sunitinib, another multikinase inhibitor, was approved a month later.

“When sorafenib was a phase I drug, I had a patient who was a former NBA basketball player and had RCC,” Vogelzang recalled. “I put him on the drug, and his cancer stopped growing. It was pretty impressive, and it was the very beginning of the field of targeted therapy for RCC.”

Further excitement has recently come with a compound Vogelzang is testing in patients with castration-resistant prostate cancer: radium-223 (Alpharadin), which targets bone metastases.

“The first time I used it in a patient, I saw that, a month later, his pain was gone and his PSA [prostate-specific antigen] was down,” the doctor said. “He’s still alive, and that was two years ago. You go, ‘Wow, this is impressive!’”

Research Snapshot: Developing New Treatments for Prostate Cancer

Nicholas J. Vogelzang, MD, has several projects in the works that focus on prostate cancer. In this interview, he discussed new research into several novel therapeutics.

A: You have been involved in the latest clinical research into the use of cabozantinib in prostate cancer, with an abstract presented at ASCO and a paper soon to be published in the Journal of Clinical Oncology. Please discuss the results of this work.

Q: Cabozantinib is a drug developed by Exelixis in California. They had completed a phase III study in thyroid cancer and developed a trial looking at the activity of the drug in nine different cancers (J Clin Oncol. 2011;29 [suppl; abstr 3010]). I became the principal investigator of the study through US Oncology in my role as chair of the Developmental Therapeutics Committee. The oral therapy, which inhibits MET and VEGFR2, is very exciting, because it proved to be active in prostate cancer, hepatocellular cancer, lung cancer, melanoma, and other cancers. Its activity in prostate cancer suggests to me that it will change the way we practice in that disease; it’s remarkable in that it reduces pain in the majority of men and causes dramatic improvements in the bone scans and markers of bone destruction caused by prostate cancer.

Our first trial on this has been accepted into the Journal of Clinical Oncology with David C. Smith, MD, from Michigan, as its first author. That large, phase II study demonstrated high rates of bone-scan resolution, pain relief, and overall disease control—independent of PSA changes—in patients (J Clin Oncol. 2011;29 [suppl 7; abstr 127]).

The second trial we just completed, in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), was a phase II nonrandomized expansion cohort (NEC) (J Clin Oncol. 2012; 30 [suppl; abstr 4513]). Our primary endpoint in the NEC was bone-scan response based on computer-aided quantitative assessment of bone-scan lesion area; the evaluable population was 85 patients, all of whom received cabozantinib.

The results strongly confirmed the findings of the first study. Treatment with cabozantinib resulted in high rates of bone-scan response, durable pain relief, and reductions in bone turnover markers and circulating tumor cells. Sixty percent of patients had a partial response to cabozantinib, and 28% experienced stable disease.

In subgroups, 21 of 30 patients experienced a reduction in measurable disease; 16 of 33 patients who took the Brief Pain Inventory at 4 and 12 weeks reported pain reduction that was durable for six or more weeks; and 46% decreased or discontinued narcotic use. In 59 patients with circulating tumor cells ≥5, 92% experienced a decrease of 30% or more, and 39% dropped to a circulating tumor cell level of <5 at weeks 6 or 12. Among patients with elevated serum levels, 74%, 67%, and 47% had declines on treatment of ≥30% in CTx, NTx, and bALP, respectively. Twelve percent of patients discontinued cabozantinib due to adverse events, including fatigue, nausea, and anemia.

We are now participating in a third cabozantinib trial called COMET-2. In this trial, men with mCRPC that is refractory to docetaxel, abiraterone [Zytiga], and other agents, and who have ongoing pain in spite of narcotics, are being randomized either to cabozantinib plus a placebo or mitoxantrone plus a placebo, with the endpoint being pain control.

Q: You are also helping to develop another drug that looks promising in the treatment of prostate cancer: radium-223 (Alpharadin). What are some of the details of this recent work?

A: There is a lot of excitement around radium-223, a first-in-class alpha-pharmaceutical targeting bone metastases with highenergy alpha-particles of short range, because it will advance the life expectancy of patients with CRPC. The drug is now in a post-phase III stage: It’s under FDA fast-track review, and hopefully will be approved soon. Our site in Las Vegas was one of only two USA sites that participated in the phase III trial of best standard of care plus either radium-223 or placebo, known as ALSYMPCA (J Clin Oncol. 2012;30 [suppl 5; abstr 9]). The paper has been submitted for publication, which we expect will occur shortly.

For now, I can summarize what we presented at ASCO’s 2012 Genitourinary Cancers Symposium, which is that the trial was stopped early after a planned interim analysis because data showed a significant improvement in overall survival for these patients with the addition of radium-223. The trial also met its secondary endpoints of fewer, and delayed, skeletal-related events.

Specifically, median overall survival was 14.9 months in the experimental group and 11.3 months in the placebo group, and time to first skeletal-related event was 13.6 months with radium-223 versus 8.4 months without it.

We are one of just a few sites in the US that have the drug available on an Expanded Access Program (EAP). We have treated about 20 patients now, and I can confirm that this is certainly a very promising therapy for CRPC patients with bone metastases.

Q: You are working with Stand Up To Cancer to research new treatments for melanoma. What will this project entail?

A: I’m a member of the Melanoma Dream Team, launched in late 2011 and jointly funded by Stand Up To Cancer and the Melanoma Research Alliance. The team has a $6 million, three-year grant to bring new agents to the clinic.

Our goal is to do genetic testing and profiling on melanoma patients who are not treatable with vemurafenib [Zelboraf], and find targets we could use for treating them. The patients in question, who have BRAF wild-type melanoma, and thus do not carry the mutation targeted by vemurafenib, have a poor prognosis and few therapeutic agents available to them. This project will be an attempt to change that. My role in the project will be to serve as a senior independent (non-melanoma) clinician advising Jeffrey M. Trent, PhD, FACMG, and Patricia M. LoRusso, DO, and overseeing the treatment toxicities and outcomes.

Personal Sacrifices Result

There has been, however, a downside to Vogelzang’s passion for his work. His long hours, he said, contributed to his divorce from his first wife, with whom he has three grown children.

“You don’t work that hard,” he said, “without hurting some family relationships.”

The divorce and remarriage were two of the reasons Vogelzang left his long-term post at the University of Chicago to pursue something very new. He moved across the country with his new family to help launch the fledgling Nevada Cancer Institute, becoming its 10th employee.

“I figured I had one more career left in me,” said Vogelzang, who was 55 at the time. “It was an opportunity to say, ‘OK, I’m going to take a new step in my life.’”

Vogelzang is proud of his goal in the endeavor—to increase what he saw as an inadequate level of research activity in Nevada&mdash;and happy he helped to create a “wonderful environment” at the nonprofit cancer institute, which grew to include a team of 340 faculty and staff. But, ultimately, the institute faltered as the economy entered the recession.

After five years on the job, Vogelzang said, he was told he would be replaced as director. Last year, the institute filed a voluntary bankruptcy petition, and the UC San Diego Health System stepped in to acquire its assets.

Since leaving the institute, Vogelzang has moved to CCCN in Las Vegas, where he sees about 500 new patients each year and works with more than 400 fellow oncology professionals, including 24 medical oncologists. He is the site research leader for CCCN, which is affiliated with US Oncology and the University of California, Los Angeles, and which entered more than 300 patients into clinical research studies in 2011.

Values Steered Choices

The late-career change seems par for the course in a lifetime defined by new starts.

Born in Holland, Michigan, Vogelzang, the oldest of seven children, learned early the joys and rewards of caring for others due to his upbringing in a large, closeknit family guided by the values of the Christian Reformed Church, his father’s work as a preacher in that faith, and his mother’s work as a teacher. But those ideals sometimes sparked big changes.

When Vogelzang was 5, his family moved to Utah to start churches, a school, and a mission for Native Americans. As part of the family’s commitment to helping members of their small new community, the doctor recalled, “we’d often have alcoholics or immigrants stay in our home.”

Years later, after his divorce and remarriage, Vogelzang had to find a way to cope with another major change: the loss of a child, one of his wife’s three from a previous marriage, all of whom the doctor had adopted. It was 2006, and Liz, 18, died in a car crash after falling asleep at the wheel, two weeks before she was scheduled to begin her studies at Trinity Christian, Vogelzang’s alma mater, on a soccer scholarship. “We wonder who she would have married,” Vogelzang said, “and what her kids would have been like.”

The couple faced additional challenges when Vogelzang’s wife developed cancer; she has since recovered from chemotherapy, radiation, and surgery for sarcoma, Vogelzang said. The doctor’s own experience with radiation for Hodgkin disease resulted in his undergoing coronary bypass and left him with thyroid and esophagus problems, neck stiffness, and shortness of breath.

Despite that roller-coaster series of events, Vogelzang said his career has been shaped not so much by the changes in his life, but by the aspects that have remained constant.

A theme that has stayed with him since childhood is his “adoration” for science— spurred, he said, by his father’s deep curiosity.

“For example, my dad would bring home, from a coal-miner friend, big casts of dinosaur bones—a claw or femur from a triceratops&mdash; for dinnertime conversation pieces,” he recalled. “My dad had a fondness for taking us to manufacturing plants, mining facilities, and logging activities. We went to see the Crazy Horse Memorial in South Dakota, interviewed its sculptor, Korczak Ziolkowski, and sat under the arm of Crazy Horse in the Black Hills. It was fascinating.”

The tradition of caring for others has also remained a constant in Vogelzang’s family; two of his siblings are physicians, two are nurses, one is president of Maine Public Radio, and one is president and CEO of Boston Advisors. In spite of years and distance, the family remains very close, still having regular reunions, most recently this summer in the San Juan Islands. Vogelzang believes that constancy and support have allowed him to face the challenges of change while continuing to give back to others.

The importance of those values was underscored for Vogelzang at Trinity Christian, where he majored in biology with a double minor in chemistry and philosophy. What he learned about philosophy, he said, has affected his outlook ever since.

“It gave me a real guiding light to understand that each of us stands on a certain set of ethical and spiritual principles, and we have to choose what we believe,” Vogelzang said. “Out of that belief come our science and our business and our practical life. Where we start and what our core beliefs are influences everything in the rest of our lives.”