Study in JAMA led by University of Maryland School of Medicine researcher concludes that new, more effective systemic treatments are needed to combat spread of disease
Researchers have found that adding the drug gemcitabine to standard chemotherapy and radiation following surgery improved survival for patients with the most common form of pancreatic cancer, according to a new study published in the March 5 issue of the Journal of the American Medical Association (JAMA). The study focused on patients with pancreatic head adenocarcinoma, or cancer of the head (the wider part) of the pancreas. But researchers concluded that new, more effective systemic therapies still are needed to prevent recurrence of this often-deadly disease.
The four-year, multicenter study was the largest clinical study of its kind and the first Phase III trial in the United States in three decades to look at additional (adjuvant) treatment for pancreatic surgery patients. "This study will change standard practice across the country for post-operative treatment of this type of pancreatic cancer," says the principal investigator, William F. Regine, M.D., professor and chairman of radiation oncology at the University of Maryland School of Medicine and chief of radiation oncology at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.
The research was conducted under the auspices of the national Radiation Therapy Oncology Group and funded by the National Cancer Institute (NCI). "Although the results are not considered statistically significant, they are clinically meaningful. There was consistent improvement in survival among patients with cancers of the head of the pancreas who received gemcitabine, at least up to three years following diagnosis," Dr. Regine says. "Given that we’re dealing with a cancer with such a high mortality rate, while this is not a home run, it would be considered a single."
Cancer of the pancreas is the fourth leading cause of cancer death in the United States, with 32,000 people dying of the disease each year. Only 4 percent of people are still alive five years after they are diagnosed. Surgery is the treatment of choice, but less than 15 percent of patients are eligible because the disease is usually diagnosed at an advanced stage.
Dr. Regine says that based on the study’s preliminary results, which have been reported at major cancer meetings, many oncologists already are using this new combination therapy with gemcitabine to treat patients who have had surgery known as the Whipple procedure.
Gemcitabine interferes with the growth of cancer cells and belongs to a group of medicines called antimetabolites. It is also used to treat patients with advanced pancreatic cancer who are not eligible for surgery, as well as a number of other cancers.
More than 500 patients at 164 institutions, including the University of Maryland Greenebaum Cancer Center, were enrolled in the study from 1998 to 2002, with follow-up through August 2006.
Thirty-one percent of the participants with pancreatic head adenocarcinoma were still alive three years after diagnosis following surgery and treatment with gemcitabine, another chemotherapy drug called 5-fluorouracil (5-FU) and radiation. That compares with a 22 percent three-year survival rate for patients who were treated with 5-FU and radiation alone after surgery – the standard postoperative treatment for this type of cancer since the 1980s.
The median survival for patients who received gemcitabine was 20.5 months, compared to
16.9 months for patients who received the standard treatment. Median survival is the point at
which half of the patients in each group are still living. Researchers did not see any benefit to adding gemcitabine for patients with cancer in other parts of the pancreas.
Dr. Regine says that the treatment was well-tolerated, and patients in the study had the lowest rate of cancer recurring in its original location than in any previous study. The tumor came back in the same area in 23 percent of the patients, compared to 40-60 percent of patients in other studies. But, according to Dr. Regine, 70 percent of the patients in this study experienced spread of their cancer to other parts of the body, a process that is known as metastasis.
"Clearly, metastatic disease is a huge problem, and we need more clinical research to identify new systemic or targeted therapies to prevent this type of recurrence," Dr. Regine says. He adds that researchers already are planning to test new agents, using the new combination therapy of gemcitabine, 5-FU and radiation as the standard.
They also will study the genetic profiles of these cancers to help determine how well patients will respond to a particular therapy, which would allow doctors to tailor the treatment to the individual patient. "We know from this study that there are many pancreatic cancer patients out there looking to enroll in clinical trials with the hope of finding therapies that will improve their chances," he says.
In addition to the Radiation Therapy Oncology Group, two other cooperative groups, the Eastern Cooperative Oncology Group and the Southwest Oncology Group, were also involved in the study. All three groups receive funds from the NCI.