Cancer Care that Exists Across Time Zones

Posted in GUMC Stories

Sydney Davis says she always felt she would have a story to tell. She just didn’t know it would be about being the “poster child” for the emerging era of cancer care.

Davis, of St. Louis, Mo., is living proof that oncologists around the country are teaming together in the hopes of finding the right treatment for each patient. She is the recipient of individualized cancer care — treating tumors based on their unique genetic makeup — that required the collective efforts of oncologists in three different states across the country to provide.

“I would say it takes a village to fight cancer, but in my case, my village extended across time zones,” says Davis, 47.

Her story began in May 2011, when she felt an unusual stomach ache, which became severe enough to land her in the hospital several days later. She was diagnosed with pancreatitis — an inflamed pancreas — and instructed to adopt a low-fat diet for the summer.

In September, she had a CT scan and doctors found a mass in her pancreas and cancer spots on her liver. Davis had stage IV pancreatic cancer, a diagnosis that typically offers a life span of six months to a year, tops.

But she didn’t want to hear those statistics. And with her blessing, her husband, Jeff, and extended family and friends set about to find specialists in pancreatic cancer to treat her.

Within a week of her diagnosis, she was seen at the Siteman Cancer Center at the Washington University at St. Louis and then she traveled to Houston to MD Anderson Cancer Center. Oncologists from both centers worked together to prescribe a treatment, which was a round of “chemo light,” as Davis describes it, to see how she would respond after eight weeks of therapy. The physician at Washington University also ordered a biopsy to look for mutated genes in her tumor.

The first round of chemotherapy had slowed the growth of the cancer, but not as much as the doctors had hoped, here was a beam of light however: the test revealed that Davis had a mutation in her BRCA2 gene. Now there would be something to target.

To treat cancer, knock out DNA repair

At Georgetown Lombardi Comprehensive Cancer Center, Michael Pishvaian, M.D., Ph.D., an oncologist who specializes in gastrointestinal cancers, was studying what he thought was a very exciting discovery. It had to do with a new class of cancer therapies, called PARP inhibitors, which are drugs that diminish the ability of cancer cells to fix the damage caused by chemotherapy.

Most of the time, PARP, short for “poly (ADP-ribose) polymerase,” is key to human health. It is a potent protein that helps repair the damage that is inflicted daily on our genes, from normal errors in copying chromosomes to cellular insults such UV solar light.

But many tumors learn how to turn on PARP to quickly fix the damage that chemotherapy wreaks on cancer cells.

The seminal work in discovering the function of PARP, and that PARP inhibition sensitizes cancer cells to chemotherapy was done at GUMC in the early 1990s by the late Mark Smulson, Ph.D., a professor of biochemistry.

Supported by funds from the Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown Lombardi, Pishvaian began a clinical trial to test PARP inhibitors in advanced colon cancer.

Pishvaian thought combining a PARP inhibitor with chemotherapy also might be helpful for pancreatic cancer. And he believed it might be even more beneficial if patients had a mutation in several other DNA-repair mechanisms, such as BRCA2. Someone with a BRCA2 mutation who took a PARP inhibitor would essentially have a double shut down of DNA repair tools—which would be beneficial when the damage is intentional.

“It is a dramatic irony. Having a mutation in a DNA repair gene makes a person more susceptible to cancer, but it also helps chemotherapy work better,” Pishvaian says. Researchers now know that up to 5 percent of pancreatic cancer cases are due to a faulty DNA repair gene.

So, supported by funds provided by the Ruesch Center, Pishvaian launched a clinical trial to test chemotherapy and a PARP inhibitor in patients with pancreatic cancer, whether or not they had a mutation in DNA repair genes

The first patient to go on his trial — the only one of its kind in the nation at the time — was enrolled in January 2011.

The Good News

Back in St. Louis, Davis was still on her first regimen of therapy, but her doctors, family and friends ran with the news that she had a BRCA2 mutation. They soon found out about Pishvaian’s clinical trial testing a PARP inhibitor in pancreatic cancer for patients with a BRCA 2 mutation. The Georgetown Lombardi oncologist received a call over the weekend about Davis, and within several days, she was in his clinic — and enrolled in the study.

For two months, every other week, she flew to D.C. to receive the PARP inhibitor and her chemotherapy infusion via a pump. She would fly back with the pump still dispensing chemo, and send it back via FedEx after 48 hours. “It was important for me to be at home, with my two children, age 11 and 14. But it was rough,” Davis says.

Shortly after starting the trial, her Washington University oncologist was able to administer the treatments in St. Louis, under a compassionate care program and in consultation with Pishvaian.

Good news has recently rolled in. In late July, Davis had a CT scan at MD Anderson Cancer Center, and no tumor was seen in her pancreas and no cancer spots were detected on her liver. A PET scan also showed no “hot cells” or active cancer cells.

“I am not out of the woods yet, and I am not using the word cure,” Davis says. “But I am in miraculous, unchartered territory.”

She hopes the treatment will work for her father, who has also just been diagnosed with pancreatic cancer. And her paternal grandmother died of ovarian cancer, which is sometimes caused by a BRCA2 mutation. Davis believes it is possible the BRCA2 mutation has been passed down for generations.

“Sydney sought us out, and we are so glad about that,” says Pishvaian. “It speaks to the idea that the cancer treatment network, and patients, are able to find the right clinical trial for them — even if it is across the country.”

Davis wants to make sure cancer patients know something else. “Don’t listen to bleak statistics. Do your research and get to the right doctor first,” she says. “Most of all, reach out to your family and friends. It takes a very large village to tackle cancer.”

By Renee Twombly, GUMC Communications

(Published Sept. 12, 2012)