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    Bench to Bedside Podcast: A Clinical Trial Offers New Hope for a Young Cancer Patient


    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.

    While visiting family in Honduras, Casco, now 36, had a suspicious mole removed. A biopsy of the mole showed that Casco had melanoma, a potentially deadly skin cancer. When she returned to New Hampshire, a PET scan showed no signs that the cancer had spread. Still, she cancelled a planned move to Florida to remain close to her doctors.

    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.

    Ernstoff explained her treatment options: chemotherapy, which would provide a limited benefit, or Interleukin-2 (IL-2) immunotherapy, a treatment that uses injections of a cytokine signaling molecule that is part of the body’s natural response to a microbial infection to fight off the cancer.

    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.

    Alejandra Casco initially received immunotherapy to treat her Stage 4 melanoma but it was not completely successful.
    Alejandra Casco initially received immunotherapy to treat her Stage 4 melanoma but it was not completely successful.

     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.”

    Unlike the IL-2, the trial medication did not take a huge toll on Casco’s body, but she was impatient as months turned into a year and wanted it to be over. “But I realized [thinking this way] wasn’t good for me; I just needed to surrender that time,” she said.

    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 writing group with other patients. 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.

    Casco at Dartmouth-Hitchcock Medical Center, her cancer now in remission following her enrollment in a clinical trial.
    Casco at Dartmouth-Hitchcock Medical Center, her cancer now in remission following her enrollment in a clinical trial.

    Ernstoff, no longer at Dartmouth-Hitchcock, is now professor and chief of the Division of Hematology/Oncology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences and chair of the Department of Medicine and senior vice president of clinical investigation at Roswell Park Cancer Institute.

    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 AAMC Research Means Hope campaign promoting the value of medical research and advocating for sustained, predictable federal funding for the NIH.