Two Experimental Drugs Show Promise for Rare Pancreatic Cancer
WEDNESDAY, Feb. 9 -- A pair of tumor-inhibiting drugs more than doubled the progression-free survival time for patients with a rare type of pancreatic cancer, according to two new studies.
In separate phase 3 trials by French and American scientists, the drugs everolimus and sunitinib extended the survival of participants with advanced pancreatic neuroendocrine tumors from about five months to 11 months.
Also known as islet cell carcinoma, this type of pancreatic cancer represents a small proportion of all such malignancies but has a better prognosis than adenocarcinoma, the more common and deadlier form. Fewer than 20 percent of adenocarcinoma patients are still alive one year after diagnosis, according to the American Cancer Society, while the study authors said the median survival of neuroendocrine patients is 27 months.
Both studies were reported in the Feb. 10 issue of the New England Journal of Medicine.
"I had a pretty good feeling about the study," said Dr. James Yao, lead author of the everolimus research and deputy chair of gastrointestinal medical oncology at the University of Texas M.D. Anderson Cancer Center. "This is certainly what we were hoping for. I think the magnitude of the treatment difference was very good to us."
The new medications, which are awaiting U.S. Food and Drug Administration approval, work by inhibiting growth factors in pancreatic neuroendocrine tumors -- the same cancer for which Apple CEO Steve Jobs was treated in 2004.
The everolimus study, funded by the drug's maker, Novartis Oncology, analyzed 410 patients from 82 health centers in 18 countries worldwide. All patients had either inoperable or metastatic neuroendocrine pancreatic tumors and were randomly assigned to receive either everolimus (10 milligrams daily) or a placebo.
The sunitinib study, funded by drugmaker Pfizer, had 171 participants also randomly assigned to either the medication (37.5 milligrams daily) or a placebo. Enrolled at 42 centers in 11 countries, these patients also had advanced disease.
The primary endpoint of each study was progression-free survival, defined as the time between the start of the research until evidence of cancer progression or death from any cause.
"This is not the garden variety pancreatic cancer we see commonly. It's a rare tumor but definitely a health care issue," said Dr. Bhoomi Mehrotra, section head of the medical oncology and stem cell transplantation program at North Shore-Long Island Jewish Medical Center in New Hyde Park, N.Y.
"Obviously, this is very encouraging, particularly for patients who are having disease progression," Mehrotra said.
Citing ethical considerations, the everolimus researchers allowed 148 placebo patients whose cancers had spread during the study to switch to the active drug. About 64 percent of everolimus patients experienced some degree of tumor shrinkage from the drug, compared with 21 percent receiving the placebo.
Sunitinib performance was similarly impressive, prompting the researchers to discontinue the study early after noting the radical increase in progression-free survival for those on the active drug.
"There certainly is the potential for patients to be on this [everolimus] for a long time," Yao said, noting that he does not yet know the drug's potential cost. "About 34 percent of patients were alive and progression-free after 18 months, compared to 9 percent of untreated patients. So the curve separated very early."
Side effects, some of them severe, were common with both drugs and included diarrhea, fatigue, anemia and low white blood cell counts.
Noting that the medications might be able to be taken indefinitely if still effective, Mehrotra questioned whether the side effects would outweigh the benefits for patients with either no symptoms or stable cancers.
"It remains an open question of when therapy should be initiated . . . and how we sequence the therapies coming down the pike," he said. "Since these patients live for several years, although the side effects were manageable, this [everolimus] study does raise questions about the optimal timing, dosing and duration of treatment."
To learn more about pancreatic neuroendocrine tumors, visit Stanford University School of Medicine's Cancer Center.
Posted: February 2011
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