March 29, 2013
By Kari Bohlke, ScD
It’S a popular term these days: personalized medicine. But what does it actually mean? In the case of cancer, personalized treatment involves using the specific characteristics of the cancer and the patient to guide treatment decisions. The goal is to identify in advance the treatments that are most likely to be effective for a given individual. Although this idea is not a new one, our ability to achieve it is growing as researchers identify new biological pathways that contribute to cancer growth and new drugs that target these pathways.
Here are a few examples:
Roughly 5 percent of non–small cell lung cancers contain an abnormal version of a gene known as ALK. Patients who test positive for this genetic change tend to benefit from a targeted drug known as Xalkori® (crizotinib).
Melanomas that test positive for a particular mutation in the BRAF gene tend to respond to a targeted drug called Zelboraf ® (vemurafenib).
For women with early-stage, estrogen receptor–positive breast cancer, the Oncotype DX® test provides information about risk of recurrence and need for chemotherapy.
Research in personalized cancer care is challenging—cancers can be driven by multiple, complex biological pathways— but progress is clearly being made. And when tests are available to guide treatment decisions, patients can benefit no matter what the test result. If you learn that you are not a candidate for a particular treatment, for example, you can avoid the side effects and the cost of that treatment and focus your attention on other approaches that are more likely to be effective.
These tests do not replace a discussion of treatment options with your physician, but they do allow for a more informed discussion. Factors other than test results— such as your individual needs or preferences—can also be considered.
Innovation in colorectal cancer care
The development of new, personalized cancer treatments starts with innovative cancer researchers. Edward H. Lin, MD, a medical oncologist and researcher at Seattle Cancer Care Alliance and the Fred Hutchinson Cancer Research Center, specializes in the treatment of gastrointestinal cancers and is studying new and more-effective ways to treat colorectal cancer. He’s particularly interested in the role of cancer stem cells in cancer growth and resistance to treatment. “It’s an emerging field,” he explains. “These are cells that may have escaped chemotherapy, and a higher number of these cells predicts worse outcomes for the patient.”
A treatment that Dr. Lin is studying involves a combination of two drugs that are taken orally (by mouth): Xeloda® (capecitabine) and Celebrex® (celecoxib). Xeloda is a chemotherapy drug, and Celebrex is a nonsteroidal anti-inflammatory drug (NSAID) that is commonly used for such conditions as arthritis. Interestingly, the combination of these two drugs improved colorectal cancer outcomes by targeting cancer stem cells in some of his patients.
“We’ve already treated more than 100 patients,” says Dr. Lin. The result so far: promising response rates and survival among people with advanced colorectal cancer. As an added benefit, the addition of Celebrex to Xeloda reduces one of the frequent side effects of Xeloda: hand-foot syndrome, a condition that involves redness and swelling in the hands and the feet.
To further evaluate the combination of Xeloda and Celebrex, Dr. Lin is conducting a phase II clinical trial with funding from the Gateway for Cancer Research, a nonprofit organization that funds innovative, patient-centered cancer research on both conventional and complementary cancer therapies. “We’re using the Gateway funding to prospectively prove that you can induce complete remission in patients with colon cancer,” says Dr. Lin. The study will compare Xeloda and Celebrex with standard chemotherapy among patients with metastatic colorectal cancer that has responded to initial chemotherapy. The study will also explore whether certain biologic markers can predict which patients are likely to respond to the novel treatment.
The Other Part of the Equation
Researchers can’t take all of the credit for advances in cancer treatment. The patients who participate in clinical studies and who try new approaches to treatment are a key part of the process.
Gail Shugart, of Alpine, Texas, has been treated for metastatic colorectal cancer by Dr. Lin. Although Gail’s story does not prove that Xeloda and Celebrex provide a benefit—definitive information about the safety and the efficacy of this treatment requires final results from large studies—it does illustrate some of the challenges and decisions that a person confronting the limits of standard treatments must face.
When Gail was first diagnosed with colon cancer in the fall of 2004, the cancer had already spread to her liver. “I was 59,” she says. “I didn’t really pay attention to some of the signs.” She received conventional treatments such as surgery and intravenous chemotherapy and was also treated with Xeloda and Celebrex by Dr. Lin, who was then at the MD Anderson Cancer Center. Together these treatments eliminated all signs of cancer.
In spite of this good response to initial treatment, the cancer later returned— twice—in one of her lungs. Surgeons were able to remove the lung metastases, but Gail found that she couldn’t tolerate the additional intravenous medications. “I was so sick,” she recalls. By this time Dr. Lin had moved from Texas to Washington State, but Gail was determined to take charge of her own care: “I got on the Internet and looked for his name because I remembered that he was doing something different.” She traveled to Seattle to see him and repeated the treatment with Xeloda and Celebrex that she’d received earlier in the course of the disease. She was free of detectable cancer at the time she began this treatment—and remains so.
Gail understands that the combination of Xeloda and Celebrex is still under study, but she feels good about working with someone who is actively researching the topic. “He’s an independent thinker,” she says of Dr. Lin, “and he just wants to save lives.”
What It’s All About
Ultimately, personalized cancer care is about the person. When asked what motivates him, Dr. Lin responds, “It’s just really gratifying. My family has been touched with colon cancer, and I’ve seen a lot of patients over the years. It’s certainly these patients who inspire me to do what I do today.”
Organizations such as Gateway that fund innovative cancer research share this focus: the organization’s research mission is to support patient-centered research that improves cancer treatment outcomes and restores the cancer patients’ quality of life.