Chemo and radiation after surgery prolongs life for pancreatic cancer patients

Pancreatic cancer patients treated with a combination of chemotherapy and radiation after surgery survive approximately six months longer than those receiving surgery alone, Johns Hopkins Kimmel Cancer Center scientists report.

Previous clinical trials conducted in the 1980s and 90s in the United States established the benefit of postoperative chemotherapy and radiation. However, experts still disagree on whether to administer the treatments because results from European studies suggest the opposite effect - a decrease in survival.

"Some physicians might avoid chemotherapy and radiation if a benefit in survival is uncertain. However, without proof, I believe it is a disservice to these patients if we eliminate chemotherapy and radiation," says radiation oncologist Joseph Herman, M.D., who led the study.

Herman and his team sought to put the issue to rest by reviewing records of 616 Johns Hopkins patients whose pancreatic cancers were surgically removed between Aug. 30, 1993, and Feb. 28, 2005. The researchers compared the survival of 345 of the patients who had only surgery with 271 who were then treated with 5-fluorouracil (FU)-based chemotherapy agents and modern types of radiation.

Patients receiving the combined chemotherapy and radiation experienced an improved median survival when compared with patients who did not (21.2 vs. 14.4 months). Two-year survival also improved (43.9 percent vs. 31.9 percent), as did five-year survival (20.1 percent vs. 15.4 percent). Results will be published in the July 20 issue of the Journal of Clinical Oncology.

"The take-home message of this study is that patients who received combined chemotherapy and radiation appeared to have better survival than patients who have surgery alone, suggesting that it is safe and beneficial if it's done carefully and properly," says Herman, assistant professor in the Department of Radiation Oncology and Molecular Radiation Sciences.

He cautions that this is a retrospective study and that selection bias was possible as they may have selected out those patients who are healthy enough to receive the chemotherapy and radiation. "Regardless, it is still encouraging to say that many of these patients had very aggressive cancer and a lot of them are still alive several years after they received this combination therapy," says Herman.

Because data to assess treatment toxicity were unavailable, Herman and his study team focused on survival instead. He says the majority of patients were able to complete the therapy, suggesting that they tolerated it well.

The study also identified risk factors to determine those patients most likely to benefit from combined chemotherapy and radiation. Patients who clearly benefited included those with lymph-node-positive disease and those with tumors larger than 3 centimeters (about 1.2 inches). Patients with aggressive tumors also benefited, as did those with margin-positive disease, where the surgeon was unable to remove most of the tumor.

Groups were similar with respect to tumor size, nodal status and margin status, but those receiving combined chemotherapy and radiation were younger (median 64 vs. 70 years) and less likely to present with another serious disease.

"The survival benefit is still seen regardless of high-risk tumor characteristics and after controlling for age, other concurrent diseases and surgical complications," Herman says.

Patients in this study received about five and a half weeks of combined chemotherapy and radiation, which is referred to as concurrent therapy. The therapy begins about four to eight weeks after surgery.

Most patients also received continuous-infusion 5-FU chemotherapy. This is a form of chemotherapy that enhances the ability of radiation to damage DNA, the building block of the rapidly dividing cancer cells. Patients take four weeks off at the conclusion of their initial therapy, and then may receive maintenance chemotherapy, as prescribed, in the weeks and months ahead.

Pancreatic cancer strikes about five out of 100,000 people each year in the United States. Because pancreatic cancer often has no symptoms in its early stages, cancerous tumors often go unnoticed until the cancer advances and individuals become ill. Prognosis is poor for long-term survival, with only about 5 percent of pancreatic cancer patients surviving five years after their diagnosis.

The most aggressive and effective form of treatment for pancreatic cancer is a complicated surgery commonly known as the Whipple procedure (used in this study), in which the gallbladder, common bile duct, part of the duodenum, and the head of the pancreas are generally removed. Johns Hopkins Hospital has performed more than 3,000 Whipple surgeries over the past 25 years.

The study was funded by the Johns Hopkins Department of Radiation Oncology and Molecular Radiation Sciences.

Michael Swartz, Charles Hsu, Jordan Winter, Timothy Pawlik, Elizabeth Sugar, Ray Robinson, Daniel Laheru, Elizabeth Jaffee, Ralph Hruban, Kurtis Campbell, Christopher Wolfgang, Fariba Asrari, Ross Donehower, Manuel Hidalgo, Luis Diaz, Charles Yeo, John Cameron, Richard Schulick and Ross Abrams, also from Johns Hopkins, assisted with this study.

http://pathology.jhu.edu/pancreas/ and http://jco.ascopubs.org/