Many Americans, including Alejandra Casco, owe their lives to clinical trials. When standard courses of treatment don't prove helpful, patients and their care providers turn to trials. In many cases, trials help these patients and, later, countless others with the same disease or condition by advancing new therapies and treatments.
In 2010, Casco and her family were living in Manchester, N.H., having emigrated from Honduras, in Central America, where she was born. That year, a trip back to her birth country would change her life forever and start her on a path to a long-term involvement with medical research.
Tuesday, July 18, 2017
Bench to Bedside Podcast: Alejandra Casco
As the year went on, Casco began to feel weak. A second PET scan showed less favorable results. The cancer had spread to her lungs, liver, and bone; her diagnosis was Stage 4. She was referred to Dartmouth-Hitchcock Medical Center where oncologist Marc Ernstoff, MD, reviewed her case.
Monday, July 17, 2017
Learn Serve Lead 2017: The AAMC Annual Meeting
LSL, scheduled for Nov. 3–7 in Boston, will feature content on medical research.
- Participating in Biomedical Research: Protecting Human Subjects and Engaging Individuals on Saturday, Nov. 4, from 10:30-11:45 a.m. Explore issues related to the paternalistic view of research subject participation and protection along with the benefits and challenges of engaging patients in the research process with changes in the research and regulatory landscape from the Common Rule.
- Making the Case for Medical Research on Sunday, Nov. 5, from 1:15-2:30 p.m. Explore successful strategies and opportunities to engage nontraditional partners to help demonstrate the wide-ranging benefits of public investment in medical research, including improved health outcomes and economic impact.
IL-2 was originally researched and developed in the 1980s by the National Cancer Institute of the National Institutes of Health (NIH) and adopted in the mid-1990s as a standard therapy for both melanoma and kidney cancer. The cytokine involved in IL-2 treatment induces what is known as cytokine storm, a syndrome in which the immune systems activates too many immune cells in one place. In response, a patient’s blood pressure drops, body organs may appear to fail, and body weight may increase by 10%. “It’s a pretty miserable treatment to get through,” said Ernstoff.
Casco remained hopeful and opted for treatment with IL-2, starting her first six-day cycle in July 2010. She received an infusion of the immunotherapy every eight hours during each cycle until the side effects—dizziness, reduced appetite, itchy and peeling skin, fluid retention, and weight gain—became too much for her body.
“The way I always describe this, as with many therapies, is that you’re in a driver’s ed car, and you both—the physician and the treating team, as well as the patient—have the controls,” Ernstoff said. The physician may accept some of the toxicities as safe, he said, but the patient may not want to continue. “It’s sort of a shared decision-making process with each dose of therapy.”
Casco would proceed with another three cycles (one in August and two in December) and complete her treatment in January 2011. Her next set of scans, taken in March, showed that almost all the tumors had shrunk. Almost all.
Clinical trials: The last stop for some patients
One tumor in Casco’s lung was not responding to the IL-2 therapy. The only treatment option left was available only through enrollment in a clinical trial. Ernstoff suggested a particular trial based on knowing the mutation in the BRAF gene associated with her cancer. He was optimistic about the treatment being used in the trial from early reports on targeted therapies. However, some patients responded well only for a short time.
“The conflict of interest we have as physicians ... is we have our primary responsibility to the patient. But we also have a responsibility to [help] the population of patients with that disease,” said Ernstoff. “Only through that research and understanding can we improve our life expectancy and the quality of our lives.”
Casco summoned her resolve. “If there was a clinical trial, and I could do something positive, whether it was for myself or somebody else, then all I could do was go forward,” she recalled thinking.
Every week for eight weeks, Casco would travel for an hour and fifteen minutes—even longer in the winter—from her home to Lebanon, N.H., to receive new doses. After a weeklong break, the cycle would begin anew. This would go on for four years.
Casco was among 100 people who registered for the Phase 1 trial, funded by the drug’s manufacturer, which tested a multi-kinase inhibitor for use on advanced stage solid tumors. The basic science principles underlying kinase inhibitors were developed over many years using, in part, NIH funding.
“With the prolonged time from when the experiments start until a usable discovery appears, basic science research cannot promise a predictable return on investment. Industry rarely conducts this type of research, leaving it to the public sector including NIH,” noted Ross McKinney, MD, chief scientific officer at the AAMC. “Industry then translates findings from the public sector’s basic research into marketable drugs or molecules optimized for pharmacological use, as they did in this case. The next breakthrough could come from anywhere.”
Monday, July 17, 2017
Clinical Trials 101
Clinical trials are conducted in phases. Each phase provides answers to different questions about a drug or treatment.
- Phase I: The safety an experimental drug or treatment is evaluated and side effects identified. A small group of 20 to 80 people participate.
- Phase II: The experimental drug or treatment is administered to 100 to 300 people to determine its effectiveness and further evaluate its safety.
- Phase III: A large trial population (1,000 to 3,000) is used to confirm the effectiveness of the experimental drug or treatment, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow it to be used safely.
- Phase IV: After the drug or treatment is FDA approved and made publicly available, researchers track its safety, seeking more information about risks, benefits, and optimal use.
Her relationships with care providers and staff were key in helping her remain positive throughout the long treatment trial, Casco added. In addition to Ernstoff, Casco remembers nurses who would ask about her recent trips, talk with her nieces, and offer encouragement during treatment. “It definitely helped me because I could just be myself and not put up any walls,” she said.
Casco also enrolled in a. She shied away from journaling at first but then discovered writing was useful. “It really has helped me to process certain things,” she said.
In time, Casco’s scans showed only what appeared to be scar tissue. The medicine from the trial had worked, yet she continued taking a reduced dose because no one could say whether the cancer would return if she stopped the treatment. With the dosage reduction, Casco could again take the time to enjoy listening to music, reading, and being with the people around her.
Research means hope
Eventually, in 2015, while visiting her sister, Casco felt it was time to come off the trial. “I remember watching several sunrises and sunsets, and I just finally had that peaceful moment where I knew… knew that I could go back home to New Hampshire, call my doctor, and finish this clinical trial. I knew that it was done,” said Casco, who continues to enjoy her cancer remission.
Both Casco and Ernstoff today stress the value of biomedical research in treating cancer and opening up new medical possibilities for other Americans with the disease. “It is absolutely critical that we have support from the country, through our taxes and, ultimately, through NIH, to support research,” said Ernstoff, citing the need for research of common conditions, such as diabetes and obesity, as well as rare diseases. “The only way we can advance therapies for the patients with a disease in the next generation is to ask the current generation to participate in trials.”
This article is part of the Bench to Bedside Podcast series, which presents stories of patients who have benefited from medical research. The podcast series supports the AAMCcampaign promoting the value of medical research and advocating for sustained, predictable federal funding for the NIH.