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Elizabeth Jaffee
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New Weapons Battle Pancreatic Cancer

Hopkins researchers are taking on this deadly disease on several fronts. Here are two: Gene Therapy: “Even with our best treatment, the five-year survival for pancreatic cancer patients is a dishearteningly low 10 percent,” says oncologist Elizabeth Jaffee, M.D. “We had no doubt that we had to try something different.”

Buoyed by her tests of a genetically engineered vaccine in patients with renal cancer, Jaffee has begun Hopkins’ first trials of a therapeutic gene vaccine for pancreatic cancer. Like any good vaccine, this one focuses on boosting patients’ immune response to abnormal cells, but aims to work after malignancy has a foothold.

Extracting cancer cells from the pancreatic tumors of two Hopkins surgical patients, Jaffee established those cell lines in culture. She then inserted genes for the immune-stimulating protein GM-CSF into the cells and eased small numbers of them—now made harmless by irradiation—into patients via injection. The cells migrate to lymph tissue where they ostensibly spark an immune cascade ending in T cells targeted to pancreatic tumor cells anywhere in the body.

Several months into the trials, each of nine patients shows no signs of harm from the vaccine. But, more important, the pa-tients appear able to mount an immune response to their own tumor cells. When Jaffee tries a skin test—injecting patients with small numbers of their tumor cells reserved from surgery—the patients mount “the impressive signs of a classic immune reaction. We’re happy to see that 2-centimeter swelling at the injection site,” she says. “No such reaction appeared in patients before the vaccine.”

Because the test requires a patient’s own tumor cells, Jaffee says, people in the trials must first have surgery here at Hopkins. Six weeks after tumor surgery, patients get the vaccine. “But because the trials exist alongside standard treatment for pancreatic cancer,” says Jaffee, “patients have follow-up sessions of radiation or chemotherapy before a second vaccination.” She adds: “We’re really enthusiastic about this vaccine and are looking to begin the efficacy trials early next year.”

Finely tuned Adjuvant Therapy:

The fact is, far fewer people develop pancreatic cancer than, say, lung cancer—some 29,000 as opposed to 171,000 projected for this year. But because the disease is so difficult to treat and only 3 to 4 percent of patients are, by definition, cured, its mortality pushes it way up there with the biggies. Pancreatic cancer is the fourth leading cause of cancer death.

“Such figures breed a certain nihilism among oncologists,” says associate professor of oncology Ross Abrams, M.D., “and some would say that adjuvant therapy for pancreatic cancer isn’t effective.” But a team of Hopkins clinicians has a different view. “We are believers, based on experience here,” says Abrams, “that people who’ve had adjuvant therapy clearly do better than those who haven’t.”

Last year, the team of eight surgeons and medical and radiation oncologists began an in-house study of adjuvant therapy for the disease, fine-tuning combinations of radiation and chemotherapy to optimize survival after a pancreaticoduodenectomy (the Whipple procedure).

The new protocol follows the Hopkins tradition of improving the tools at hand. An earlier study of adjuvant therapy showed it could increase median patient survival from about 10 to 22 months. “That’s still too low, we think,” says Abrams. “So we’ve built upon what we learned in this new protocol.”

The approach uses chemotherapy combined with a split course of radiation therapy (two weeks of radiation followed by two weeks of rest and then two more weeks of radiation.) “The strength of the treatment has been increased on both the radiation and chemotherapy sides,” Abrams explains, “and the radiation is slightly more intense than what’s typical, but patients deal well with it.” Next comes four cycles of chemotherapy—5 FU, mitomycin and two enhancing agents, leucovorin and dipyramidol—without radiation, for a total of six months of treatment.

“We’re trying to offer pa-tients something not right off the shelf, something you can’t get everywhere,” Abrams adds, “and though the study hasn’t yet reached 10 months, it looks promising. “We believe we’re making slow but definite progress.”

--MC





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