Pancreatic cancer: Back to basics
Dana-Farber researchers and their Harvard collaborators are probing the genetics of this stubborn disease
By Richard Saltus
Diagnosed in 2000 with pancreatic cancer, Roselinde Dole has connected with Dana-Farber physician Robert Mayer, MD.
Long, flat, and fish-shaped, the pancreas lies deep in the abdomen between the stomach and the spine, in a neighborhood crowded with blood vessels and adjacent organs. Most people couldn't tell you where it is or what it does, but the pancreas is a vital part of the digestive system that also produces insulin. When cancer strikes this deeply buried structure, however, there's no palpable lump and, for far too long, few symptoms or pain to sound an alarm.
Its insidiousness makes pancreatic cancer the fourth leading cause of cancer death in the United States. The sole definitive treatment is surgery, but only 15-20 percent of patients are diagnosed early enough to warrant the risky operation. A small minority survive for years, and a rare few are cured.
Following surgery, or when the disease has spread, oncologists deploy their other weapons — chemotherapy and radiation — in an effort to add weeks or months to the average survival of six months after diagnosis.
Treating pancreatic tumors, however, is like attacking an enemy holed up in a concrete bunker. "In response to cancer, the pancreas forms a tough, fibrous protective barrier around itself, almost like a Gardol shield," says Robert Mayer, MD, referring to the "invisible shield" in a vintage toothpaste ad that could deflect flying golf balls. "It's difficult to get drugs and radiation to the tumor." Mayer directs Dana-Farber's Center for Gastrointestinal Malignancies.
For the 80 percent of patients whose conditions are inoperable, combinations of radiation and chemotherapy (the standard drug is gemcitabine) can extend life somewhat and reduce pain. Increasingly sophisticated palliative therapy helps ease the end stages of pancreatic cancer. But the stark facts remain: the American Cancer Society projects 32,180 cases of the disease in 2005, and an almost equal number of deaths — 31,800. Only 24 percent of patients live a year after diagnosis, and just 5 percent survive five years or more.
With increased attention and funding, research on pancreas cancer is drawing more scientists with insights from other fields of medicine. Federal funding has risen, and voluntary organizations such as the Lustgarten Foundation and the National Pancreas Foundation support investigators (including some from Dana-Farber) and sponsor conferences where researchers exchange the latest ideas in the field.
Clinical trials at DFCI and elsewhere are testing combinations of gemcitabine with new and old drugs, and advances such as the first mouse model of pancreatic cancer are stimulating basic research. While the benefits to patients so far are modest, some are living longer.
Roselinde Dole of Plymouth is one. "I've really beaten the odds," says Dole, a patient of Mayer's. At age 70, she's living an active life four-and-a-half years after her diagnosis in 2000, which was made early enough to receive the standard "Whipple" operation. In this procedure, named after the physician who developed it, surgeons remove the head of the pancreas and nearby structures, including the gallbladder, common bile duct, and part of the duodenum and stomach.
Dole's cancer has metastasized to her lungs and liver, though the spots on her X-rays remain small. Today she receives gemcitabine three times a month in a protocol comparing a 150-minute infusion with a standard half-hour one. In some trials, the longer "fixed-rate" infusions seem to have modestly lengthened survival in certain patients.
In the past several decades, investigators have tried surgery, radiation, and chemotherapy in many different combinations. Some medical centers are reporting encouraging results with different regimens, but so far none has proven convincing enough to alter the standard practice.
"Real progress isn't going to come by just throwing this drug or that drug at pancreatic cancer," says Mayer. "It's going to come with a better understanding of the molecular underpinnings of the disease. It's really back to the drawing board."
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