After her mother is diagnosed with gallbladder cancer, a journalist researches how to help find effective therapies for patients who get rare diseases.
By Amy Dockser Marcus
We were at one of our meetings with my mother’s oncologist. The first round of chemotherapy to treat her gallbladder cancer had failed. The latest CT scan showed a new tumor growing in her liver. I looked down at the floor, afraid to meet my mother’s eyes. I didn’t want her to know how frightened I felt.
“We have a lot of options left to try,” the doctor assured us. He started to list the drugs available to her—Avastin, Tarceva, Erbitux, Herceptin, Nexavar. He rolled out all the familiar names, part of the promising arsenal of new targeted therapies that were transforming the way cancer got treated.
But when we asked about how gallbladder cancer patients fared on these drugs, the doctor’s reply was chilling. Even major cancer centers like the one in Boston wheremymother was treated saw perhaps only a handful of patients every year with her type of cancer, and the centers didn’t pool data about patient outcomes or response to drugs.
Few researchers studied such a rare cancer, so doctors still had no idea what drove the disease. Any drugs she got would be borrowed from what worked for other cancer tumors. He hoped they might be effective with gallbladder cancer, too. But would they? Another doctor summed up our predicament: “We’re in the realm of theory here.”
Unlike breast or prostate cancer, gallbladder cancer is exceedingly rare, and because of this rarity it’s called an orphan disease. The National Institutes of Health (NIH) defines an “orphan disease” as one that affects fewer than 200,000 individuals in the United States.
By that definition, my mother’s cancer was very rare: fewer than 10,000 people in the country are diagnosed every year with gallbladder and bile duct cancers. That means that the drug companies who develop most of the new drugs usually can’t afford to focus on these types of cancers; the market is too small, and the cost of developing a drug is so high. Researchers with novel ideas or who show interest in these usually overlooked cancers find it exceedingly difficult to get support from drug companies or the government to do research.
So a patient with a rare cancer is left, as my mother was, with a maybe, with a possibly – with a probably not. The family clings to the idea that advances in common cancers will also benefit patients with rare ones; they want to believe the notion that even though no one is studying this specific disease, new treatments developed for breast or prostate cancer will ultimately benefit their loved one, too.
As we learned, reality is usually different – although it’s difficult to get firm statistics. But here’s one that surprises most people. Rare cancers that have 40,000 or fewer diagnoses in the United States, when taken in combination, are estimated to be the fourth leading cause of death each year in this country, according to data presented at a 2007 NIH-sponsored conference on the epidemiology of rare cancers. When taken in combination, they represent 27 percent of our nation’s cancer diagnoses and 25 percent of our cancer mortalities. Death rates remain stubbornly high. The new drugs that have changed the way many of the so-called prominent cancers are treated haven’t made a tremendous difference for patients with rare cancers.
Being Rare
It was 2004 when my mother was diagnosed with gallbladder cancer, one of these rare, orphan cancers. She was sixty-two years old, a stylish dresser who loved show tunes and going to the movies. She’d studied painting when she was younger and still went frequently to the Museum of Fine Arts in Boston. She ran a program at her synagogue that taught Hebrew to adults. Every week she played bridge with a group of women she’d known for more than thirty years. On Fridays she and my father brought my two children home after school. From the room where I wrote, I’d listen to the four of them laughing, my parents pretending to be various characters that figured in the elaborate games of pretend the children invented. Every Friday night we sat down together to a dinner that my mother cooked.
There were no warning signs that she might be sick. One snowy December evening, seemingly out of nowhere, my mother suffered severe, unremitting pain on her right side, just below her ribs. The pain was so intense it was hard for her to walk without doubling over. At the ER late at night, doctors told her it was gallstones and advised her to have her gallbladder removed. She went in for what was to be a routine surgery. A week later, the surgeon called with devastating news: gallbladder cancer.
At the time, I’d been working on a project for almost a year for the Wall Street Journal, where I’m a reporter, chronicling the challenges facing patients now that new drugs enable them to live longer with cancer. One of the drugs I wrote about most frequently was Gleevec, which had been approved in 2001 and had turned chronic myelogenous leukemia (CML) from a death sentence into, for many patients, a chronic condition. About 4,600 new cases of CML were diagnosed in the United States every year, making it an exceedingly rare cancer—but now there was an effective treatment. As I continued doing research, it was the story of Gleevec that offered a glimmer of hope against the growing awareness of my mother’s dire prognosis. I wanted to know why there was no Gleevec for gallbladder cancer.
Brian Druker was the researcher and clinician at Oregon Health and Science University whose single-minded determination led to the discovery of the drug. Gleevec’s success was proof of the concept that lives can be saved by blocking a pathway that cancer cells depend on to be able to grow. After Gleevec’s phenomenal success, other researchers embraced the idea that understanding the molecular mechanisms that go wrong in cancer cells can lead to effective new therapies. But on one important level, Gleevec failed to change the research model. It didn’t lead researchers and drug companies to aggressively start studying the potential targets and pathways of all cancers. Nor did it cause policy makers to dramatically widen the focus of research and funding outside a handful of the most prominent cancers.
I called Druker and asked about Gleevec. He said that when he began his work on the drug, and knowing the odds against getting a research grant at such an early stage for a rare cancer, he didn’t apply for National Cancer Institute (NCI) funding. The initial work that bolstered his theory—and eventually led to critical support and funding from the NCI and Novartis (the drug’s maker)—came from money raised by leukemia patients themselves. I wasn’t surprised to learn that patients were his earliest supporters; their lives were the ones at stake. Druker explained that he’d made regular presentations about his work to a patient-driven foundation interested in spurring drug development. His ideas seemed to offer a way; the foundation opted to give him the funds to move the ideas forward.
I thought often about Druker’s experience. In 2007, as my mother got sicker, I applied for a Robert Wood Johnson Foundation Investigator Award in Health Policy Research. I wanted to take a leave from the newspaper to focus full time on how patient advocates might be able to help speed up therapies developed for orphan cancers and what policy changes could better enable them to participate more fully in the search for new drugs.
Looking For A Better Way
I got the grant, but a few months later, my mother passed away. At first, I wasn’t certain I wanted to continue with the project. For two years, my mother had tried the most promising new cancer drugs in the hopes that one of them might stop her type of cancer from growing and taking her life. She did all she could. Forme the experience had been like standing on the shore, watching someone you love drown before your eyes as you frantically threw rescue buoys that always fell short.
Patients like my mother were supposed to be the beneficiaries of the Orphan Drug Act, which had its twenty-fifth anniversary in 2008. It was designed to entice pharmaceutical companies to develop drugs for small size disease markets through an accelerated approval mechanism coupled with tax incentives. But for my mother and others it wasn’t enough. I remained haunted by our family experience—and by a question I hoped that the project I was embarking on might eventually answer: Isn’t there a better way to help people who get rare cancers?
In the months that followed, I met people struggling with the same issues that my mother and our family had faced. Some patients, families, and friends created foundations and channeled money into research about the specific disease.They held conferences, and they pushed scientists and researchers to collaborate in developing new therapy ideas. No matter what the approach, these patient advocates often discovered that with many rare cancers, the most rudimentary tools needed by researchers to conduct experiments don’t exist. There are no repositories for patients’ tumors, saliva, and plasma that researchers require to test research questions; no tumor cells being grown in Petri dishes to create cell lines against which drugs are tried; no animal models to test to demonstrate a drug’s effect.Without these things, it was difficult to take even the first step forward.
Josh Sommer learned this as a freshman at Duke University in 2006, when he was diagnosed with a tumor pressing on his brainstem. Doctors diagnosed him with chordoma, a rare bone cancer that affects only 300 Americans a year. Recovering from surgery to remove the tumor, he and his mother, physician Simone Sommer, read the medical literature on chordoma and quickly understood that huge gaps stood in the way of finding effective drugs to treat it. In 2006 they set up the Chordoma Foundation to help accelerate drug development. What the Sommers toldmewas what I knew from my own experience: No one except patients and their families and friends have the incentive and determination to organize and drive these kinds of rare-disease efforts.
In 2007 I toured the lab run by Christopher Austin, director of the NIH Chemical Genomics Center in Rockville, Maryland.The Sommershad been there before me. On the day I visited, robots were screening hundreds of thousands of compounds, many already approved by the Food and Drug Administration (FDA) or other regulatory agencies worldwide to use with other diseases, to see if there might be a drug that would also be effective for chordoma.
The lab’s projects mainly involved research collaborations with NIH-funded scientists at academic institutions, but about ten projects under way, including the chordoma project, follow a different path. Unlike most of Austin’s work, which had been brought to him by researchers, these projects had been jump started by patient advocates like the Sommers. In some cases, patient advocacy groups, even individuals, had raised $100,000 or more to help hire a researcher in Austin’s lab to work on creating essential tools needed in new drug development, such as screening tests to know if the drugs were having an effect on the disease. In other instances, Austin’s lab took on projects when advocates presented novel scientific questions or organized collaborations that offered a chance to make progress toward treating an orphan disease.
Not every patient can manage the search for new drugs; Josh Sommer put his college studies on hold as the foundation took up more of his time. And even though new funding is expected to enable Austin’s lab to take on more than the ten patient-driven projects currently under way, the numbers remain tiny compared with the more than 6,000 rare diseases that exist. Still, these approaches represent a start, and they promote a new and important concept: patients as active partners in the search for new drugs.
I believe this will be essential to success. Patients and their families and friends need to raise money to help fund essential projects, set up patient registries, and collect and bank tissue samples to entice researchers into the field. They can lobby government officials, bringing a sense of urgency to the need to pursue translational science and a deeper understanding of what those practical applications will mean to their lives.
The Rise Of Venture Philanthropy
The existence of the Chordoma Foundation, as well as the NIH Chemical Genomics Center lab partnerships with patient advocates, represent variations on a model that has emerged in recent years. Called “venture philanthropy,” it’s where patients put up some cash and seed promising projects, often shifting the course of research into questions likely to lead to new therapies for their own diseases. Unlike the situation my mother was in—hoping that drugs developed for other cancers might somehow work for her—the venture philanthropy model focuses on coming up with new therapies tailored for patients with specific rare diseases. The most successful of these groups not only raised cash, but they also identified the obstacles preventing drug development and set out to overcome them. This could mean coordinating a group of scientists, setting up a clinical trial network, or finding a lab to run genomic testing on specific tumors.
The Multiple Myeloma Research Foundation, which has raised more than $120 million since its founding in 1998, can point to four new FDA approved drugs and sixteen more in clinical trials for that disease that resulted from its efforts. The Cystic Fibrosis Foundation, one of the pioneers of the model, invested more than $75 million in a project with the drug company Vertex; the funding helped advance two new compounds into the development stage, then it supported the launch of clinical trials that are starting to show some hopeful results. One drug is now in Phase 3 trials, the final stage before FDA approval.
The venture philanthropy model has made a difference in drawing research attention to overlooked diseases, but it’s not as effective as it could be. Disease-specific foundations can raise large sums; very few patient advocates are able to raise that kind of money. Moreover, not all patients will want to. During those Friday afternoons when my mother cooked dinner, we often talked about whether we should set up a gallbladder cancer patient advocacy group. It was always a painful discussion. I couldn’t shake the feeling that such a group might enable us to find something we might have missed (I hoped for the drug that would save her life). But I knew what such an enterprise entailed, and as my mother’s treatment and disease progression took their toll, the prospect seemed increasingly daunting.
Moving Disease-Specific Advocacy Forward
One Friday, a few months before my mother died, it suddenly occurred to me that I was cooking dinner alone. My mother was so tired that she needed to lie down, to ensure that she had enough energy to join the children for dinner. The days of her cooking elaborate meals had ended. In our kitchen table discussions, my mother’s main argument against starting an advocacy group was that she had a narrow window of opportunity with good health, and she wanted to spend the time left with us. As her daughter, I cannot regret that choice—especially now, when I think about how much those Friday night dinners meant to me and my children.
Yet I also continue thinking about the need for disease-specific advocacy. To lower the barriers to pursuing venture philanthropy, it seems to me that government funding is needed to support patient-driven research initiatives focused on findingnewdrugs.This could, for instance, take the form of matching grants made to organizations that demonstrate they can effectively raise money and create collaborations between doctors, researchers, patients, and drug companies.
A research map to help patient advocates identify existing resources inside the government needs to be developed, too. It was by chance that the Sommers learned that Austin’s NIH lab helps patients with rare diseases, hearing about it through a network of contacts that had taken them months to build. It’s not only about allocating more resources, but about making existing ones available to more people.
Steps such as these will make the venture philanthropy model more accessible, enabling greater numbers of advocates to play a role in developing new drugs. As the number of groups increases, an online network could be created to capture what already has been done by other advocacy groups in similar situations. The only way to bring down the costs driving drug development is to create economies of scale, and that means sharing information.
Without these changes, more people will be doomed to dwell in the realm of theory that my mother lived and died in. I can tell you that it’s not an easy place to be. I still think about our final meeting with my mother’s oncologist. It was in May 2007; two weeks later she would be dead. All that was left was to make arrangements for my mother to receive home hospice care. That day, for her last conversation with her doctor, she chose to wear a bright spring hat. He complimented her on the hat. “It’s hard to give up,” my mother told him.
It still is, Mom.
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1 thought on “The Loneliness Of Fighting A Rare Cancer”

  1. Anonymous says:

    I to have been diagnosed with gallbladder cancer and have found roadblocks to proper care and information. I am trying to develop a foundation that will help fund research for this cancer as well as other orphan diseases.

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