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A CLOSER LOOK

Pancreatic cancer: Hard to diagnose, even harder to treat

Though several drug trials have failed, research is continuing.

September 28, 2009|Jill U. Adams

When actor Patrick Swayze died earlier this month of pancreatic cancer, it put a famous face on a grim disease. At 57, Swayze was young enough for his death to register shock.

Swayze had an advanced case of the disease, as the cancer had spread to his liver. It's little comfort to realize he beat the odds -- most people with this diagnosis don't live more than a year after diagnosis, and Swayze lived for 20 months.

In February, Supreme Court Justice Ruth Bader Ginsburg underwent surgery for her pancreatic cancer. Her odds for survival are much better because the tumor was small and restricted to the pancreas.

Pancreatic cancer is a relatively rare cancer, but it remains one of the most lethal. "It's a very complex disease; these people are hard to take care of, they have complicated medical issues," says Dr. Margaret Tempero, research director at UC San Francisco's Helen Diller Family Comprehensive Cancer Center. The field needs more trained practitioners and more funding for research, she says.

Here's a closer look at why the cancer has been so intractable and how researchers are working to improve treatment.

The American Cancer Society estimates that 42,470 Americans will be diagnosed with pancreatic cancer in 2009 and 35,240 will die. Survival rates are about 25% at one year and only 5% at five years, according to the Pancreatic Cancer Action Network ( www.pancan.org). (By comparison, 89% of breast cancer patients and 65% of colorectal cancer patients will live at least five years beyond diagnosis).

The best chance of survival and the only chance for cure is surgical removal of tumors. "Like any other solid tumor, the goal is to get it early, before it's invaded," Tempero says.

However, because early disease lacks obvious symptoms, only a minority of patients are candidates for surgery. And unfortunately, even after surgery the cancer often comes back. "About 20% of patients are candidates for surgery and, of those, about 20% are cured," says Dr. Edward Garon, an oncologist at UCLA's Jonsson Comprehensive Cancer Center.

Clinical studies have shown that treating patients with chemotherapy after surgery reduces the risk for recurrence.

Sometimes radiation therapy is also prescribed, although doctors disagree on its usefulness. "It's discouraging that even basic issues like this -- chemotherapy alone versus radiation and chemotherapy after surgery -- have not been entirely worked out in this disease," Garon says.

Researchers are working on ways to detect the disease earlier, because that might allow more people to be eligible for surgery.

Physical symptoms of pancreatic cancer are not very specific to the disease. They include fatigue, weight loss and loss of appetite. Sometimes, jaundice and abdominal pain occur. Diagnosis depends on imaging procedures, such as CT or PET scans or endoscopic ultrasound, but these tests cannot detect small, early-stage cancers.

Even if high-tech techniques are developed for early detection, widespread screening -- analogous to mammograms for breast cancer or colonoscopy for colon cancer -- is not practical for such an uncommon cancer. But tests might be useful in high-risk groups, such as those with a strong family history.

When disease has advanced beyond surgery's reach, chemotherapy is the standard treatment. Two drugs are FDA-approved for the treatment of pancreatic cancer: gemcitabine (marketed as Gemzar) and erlotinib (Tarceva).

Gemzar has been used for more than a decade and modestly improves symptoms and survival. Tarceva was approved for treatment of pancreatic cancer in 2005 as an adjunct to Gemzar therapy. In a 2007 study, results obtained in 569 patients were statistically significant, but the overall benefit was small: 23% of patients surviving one year after the combination versus 17% with Gemzar alone.

"It's possible that there's a subset of patients with pancreatic cancer who would derive a significant benefit from the addition of Tarceva," Garon says. Indeed, he says he has witnessed some patients surviving for a long time on the combination therapy. Unfortunately, he adds, doctors can't yet predict which patients will respond to Tarceva.

The paucity of effective chemotherapy drugs for pancreatic cancer is not for lack of testing new drugs, doctors say. But many in the field have become discouraged. "There was a flurry of phase 3 [advanced] trials being done, but because most of them were negative, I think there's a real pullback on the part of industry and scientists around the world," Tempero says. Promising drugs such as Avastin, axitinib and aflibercept failed phase 3 trials in the last few years.

Why pancreatic tumors are so resistant to chemotherapy remains unclear. One possibility is that drugs have a hard time reaching the tumor cells. Research into better drug delivery has produced nab-paclitaxel, a drug coated with a protein, albumin, that binds to a protein in the tumor cells.

A current phase 3 trial is testing nab-paclitaxel in combination with Gemzar. "Those trials are in progress, so we'll have to wait and see," Tempero says. But, she adds, earlier, smaller trials were very promising.

As with other cancers, it's becoming increasingly clear that pancreatic cancer is not a single disease but a group of diseases that look the same under the microscope but are molecularly different, says Dr. David Dawson, a pathologist at UCLA's Jonsson center. He and other pancreatic cancer researchers are heartened by the success of individualized treatment in breast cancer, which is becoming categorized and increasingly treated based on molecular differences in the tumors.

"I really think we're on the cusp of doing that kind of work in pancreatic cancer," Dawson says.

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health@latimes.com

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