Making the Cancer Journey Tolerable: Loprinzi Puts Focus on Symptoms

Charles L. Loprinzi, MD

Charles L. Loprinzi, MD may have landed somewhat accidentally into the world of symptom management research, but once he arrived, he was there to stay.

Loprinzi has dedicated his medical career to oncology, including more than 3 decades at the Mayo Clinic in Rochester, Minnesota, where he currently serves as the Regis Professor of Breast Cancer Research. Underpinning much of his work, both at the bench and the bedside, is a dogged pursuit of interventions to provide patients with relief from the debilitating symptoms that often accompany a cancer diagnosis and its treatment.

“I was going to become a surgeon when I was in the first year or 2 of medical school ... but the very first clinical rotation I had was Internal Medicine, and I found that that was much more fun than sitting in medical school classes,” Loprinzi explained.

He said that he liked all of Internal Medicine’s subspecialties, and oncology offered him a way to touch upon many of them. Moreover, oncology was a field where the challenges were plenty: “We needed progress—there were a lot of questions that needed answering.”

Throughout his life, Loprinzi relished such challenges. Then he met Charles “Chuck” Moertel when he arrived at the Mayo Clinic in the mid-1980s. Moertel also chaired the North Central Cancer Treatment Group and was looking for someone to lead symptom-control research under the auspices of the Community Clinical Oncology Program (CCOP) because, as he told Loprinzi, “the treatment people don’t want to deal with such research.”

Loprinzi described the prevailing sentiment at the time more bluntly recalling what a highly respected colleague said to him during his days as an oncology fellow at the University of Wisconsin: “We don’t do puke studies here.”

Nevertheless, symptom management into the CCOP’s work in the area of cancer prevention and control, and Moertel saw in Loprinzi a promising researcher well suited to lead the effort.

Prioritizing Symptom Research

Loprinzi agreed and has never looked back.A native of Portland, Oregon, and the second of 10 children born over a span of only 11.5 years, Loprinzi said he learned early how to make his own way and to figure things out. He worked at a young age, learned to save the money he needed for his education, and set off for college at Oregon State University, sight previously unseen, with only 2 “banana boxes” of belongings.

These early experiences helped to set the stage for a career dedicated to problem solving and tackling the side effects that patients with cancer often confront and that, for some, persist long after their therapy ends.

Symptom-management trials were virtually nonexistent when Moertel first approached him, but Loprinzi has since authored hundreds of studies focusing on oral mucositis, anorexia/ cachexia, hot flashes, and chemotherapy-induced neuropathy, to name a few areas.

Randomized clinical trials he conducted early in his career demonstrated that megestrol acetate can improve appetite and lead to weight gain in patients with anorexia/cachexia. The research also illuminated the agent’s toxicity profile. Additional research Loprinzi led showed that megestrol acetate was helpful at low doses at relieving hot flashes in women with breast cancer, another principal focus of his research over the years.

Loprinzi also sought to find a solution to oral mucositis, a frequent and debilitating side effect of 5-fluorouracil (5-FU) and other chemotherapies. Following up on a suggestion of one of the nurses he was working with in the early 1990s, he led a study giving patients snow cone-like ice chips starting 5 minutes prior to 5-FU administration and continuing for 30 minutes.

The result: a 50% reduction in mucositis, according to patient-reported outcomes; ensuing studies replicated the benefit. Cryotherapy is now recommended in guidelines from the Multinational Association of Supportive Care in Cancer—not only for patients receiving 5-FU, but for other chemotherapeutic agents as well.

Currently, Loprinzi’s research is largely focused on chemotherapy-induced peripheral neuropathy (CIPN), a big problem, he said, that can be particularly hard on patients when it persists after treatment ends. He has led multiple randomized clinical trials testing promising agents for prevention of CIPN and/or treatment of established CIPN, but, “unfortunately, neuropathy remains a major clinical problem.”

“There is a substantial minority of patients who have problems [with CIPN] later on, which can be crippling for them,” he explained, which means it is very important to watch these patients closely as they are receiving potentially neurotoxic chemotherapy and identify those more prone to it early on. At times, stopping neurotoxic chemo- therapy is in order.

Loprinzi and colleagues have explored “scrambler therapy,” a nerve stimulation process that showed some promise in initial CIPN studies. His research team also evaluated minocycline, a potentially effective drug traditionally used in the treatment of acne, which they tested in a pilot, placebo-controlled, randomized trial of patients receiving paclitaxel for breast cancer; the drug did not appear to prevent CIPN, but may reduce acute pain syndrome associated with paclitaxel.

Since those nascent studies he conducted with Moertel, the field of symptom control research has grown steadily. Grounding those trials in strong science is essential, stressed Loprinzi. This means employing scientifically rigorous methodology, pursuing findings that are publishable in prominent clinical journals, and keeping their practice-changing potential top-of-mind—not only by defining new syndromes and treatments, but also by delineating those interventions without benefit or those that may actually cause harm.

The Art of Oncology

Loprinzi has received numerous awards for his research, including the Susan G. Komen Foundation Brinker Award in 2002 and the 2005 Clinical Research Award from the Association of Community Cancer Centers. He has also been appointed as an ASCO fellow and he delivered the Charles G. Moertel Lecture, established in honor of his mentor, in 2013.Loprinzi came to understand early in his career that cancer treatment was both a science and an art. He found a forum to showcase the latter in the “The Art of Oncology” section of the Journal of Oncology (JCO). Now in its 17th year, the section remains a favorite among oncologists—offering succinct, compelling glimpses into the human side of the oncologist’s everyday practice. He is the section’s founding editor, having served in that role from 2000 to 2011.

Compassionate Honesty

Loprinzi said that at first he hesitated when JCO recruited him to be the section’s consulting editor: “I was thinking, ‘I am too busy,’ but then I realized this was an offer too good to be true, and I should just do it. It turned out to be a very educational and rewarding experience.” In addition to the regular feature in JCO, Loprinzi has edited 2 anthologies of selected essays from the series, Art of Oncology: Honest and Compassionate Responses to the Daily Struggles of People Living with Cancer, which are available as Kindle e-books.Loprinzi’s office at Mayo is on the 10th floor, but he rarely uses the elevator to get there. He said that he does some of his best thinking while being physically active, preferably outdoors. In recent years, he has vacationed with Margie, his wife of more than 30 years, and other couples on week-long walking tours in Great Britain.

The father of 3 grown children who all live nearby him—2 following his footsteps into healthcare careers—also likes to split firewood.

“I cut all of my own firewood, even in the middle of winter when it is below zero degrees outside. This is good thinking time.” He notes that when it is really cold outside, the wood splits better. It is often on these occasions that Loprinzi finds he can reflect on some of the practice and research challenges he faces every day.

Breaking issues down is a strategy that has helped him throughout his career. A case-in-point: how to determine—and convey to the patient and family—what treatment approach is right for each individual. For some individuals, the goal of treatment is to try to cure the patient. For other patients, this is not a realistic goal. But Loprinzi noted that in oncology, you “never say ‘Never’ and never say ‘Always.’” When cure is not the objective, he says that the goal is to have the patient “do as well as is possible for as long as is possible.” He further notes that this can be broken down into 4 items:

“First, we want you to have the fewest side effects as possible from the cancer for as long as possible. Second, we want you to have the fewest side effects as possible from the treatment. Third, we want you to have the longest life, and fourth, we want you to have the best quality of life.”

Loprinzi said that he does not determine which one of these 4 components is most important for each of his patients, but rather sees this approach as a framework to help guide these conversations for physicians. Importantly, it explains the issues in a way that patients and families can understand. It also can stimulate reflection on the risk—benefit profile of certain therapies—not only when to start them, but also when to stop.

“I think that there is a tendency for some physicians to treat too many patients, for too long, for too little benefit, without patients knowing it and without physicians admitting it,” he said. “There is a time for stopping cytotoxic therapy. I am convinced there is a time when chemotherapy causes net harm if it is used for too long, causing survival to be shorter than it would be without it; we do not know exactly when that is.”

The lodestar for Loprinzi’s work in caring for his patients when cure is not a realistic option is one of “compassionate honesty.” This means sitting down with his patients in the clinic, where he still spends about 20% of his time, to ascertain what their goals are as he provides a realistic assessment of their prognosis.

Always More Puzzles to Solve

Loprinzi currently leads the symptom control program of the Alliance for Clinical Trials in Oncology Group. Among its latest projects is a new multisite trial led by Jennifer Temel of Massachusetts General Hospital. Temel was the lead investigator on the seminal study, published in The New England Journal of Medicine in 2010, that demonstrated a survival benefit when early palliative care was provided to patients with metastatic non—small cell lung cancer (NSCLC).

The trial (NCT02349412), noted Loprinzi, is examining the effect of early palliative care beyond the NSCLC setting to include patients being treated for other advanced lung and gastro- intestinal cancers.

“When I started my career, very few people were focusing on symptom management,” recalled Loprinzi, “but now, it has become more popular. I can tell you that a number of practicing oncologists are very happy to hear the results of many symptom-control studies, which influences their clinical practice.”

Still, he underscored, one trial will not give a researcher all of the answers, and as one question gets answered, 10 more are likely to emerge, which is one of the features of oncology research and practice that attracted Loprinzi in the first place. “I have been very fortunate to have been associated with a number of clinical trials that have described interventions that have actually influenced clinical practice,” he said.