Study shows opioid growth factor safe for treatment of pancreatic cancer

04/20/04

HERSHEY, PA--A booster dose of a substance already found in the body appears to be safe and non-toxic for the treatment of pancreatic cancer, and shows signs of arresting pancreatic cancer cell growth in patients, Penn State College of Medicine researchers report.

"Our previous laboratory and animal studies showed that opioid growth factor, called OGF, can markedly slow down the proliferation of pancreatic cancer cells," said Ian S. Zagon, Ph.D., professor of neural and behavioral sciences, Penn State College of Medicine. "Now, in this first study of OGF in people, we've shown that administering it to supplement the body's own supply is not toxic and may help patients with this almost invariably fatal disease."

The article titled, "Treatment of advanced pancreatic cancer with opioid growth factor: Phase I," appeared in the March 2004 issue of the journal Anti-Cancer Drugs.

Cancer of the pancreas, a gland in the abdomen that makes insulin and other hormones, is the fourth leading cause of cancer death. Because pancreatic cancer is usually diagnosed after it has spread to other areas of the body, as many as 98 percent of people who are diagnosed with pancreatic cancer will die from it, and only 4 percent will live more than five years.

In laboratory studies, Zagon and his team discovered that OGF, which is involved in suppression of pain in the nervous system, also controls the production of some cells, both healthy and abnormal. Pancreatic cancer cells have OGF receptors that, when bound with OGF, inhibit additional cancer cell growth. Because cancer cells reproduce so quickly, the body can't produce enough OGF to bind all of the receptors, so cancer cell growth continues unimpeded. Zagon's laboratory work suggested that providing enough OGF in the body could bind the OGF receptors, inhibit cancer cell proliferation, and give the body's own defenses time to battle the disease.

For the Phase I clinical study, sponsored by the National Institutes of Health, Zagon's collaborator Jill Smith, M.D., professor of medicine, Penn State College of Medicine, enrolled 21 patients with advanced, inoperable, pancreatic cancer. In one group, OGF was administered intravenously in a saline solution over 30 minutes once per week. Investigators tested seven different doses ranging from 25 micrograms/kilogram (μg/kg) to 250 μg/kg. Other patients enrolled in the study were taught to self-administer 50 μg/kg doses of OGF twice per day via injection. Before, during and after intravenous infusion and the initial injected doses, vital signs were monitored and laboratory values were recorded. The study protocol was approved by the Institutional Review Board at Penn State Milton S. Hershey Medical Center under federal regulations and was conducted in the National Institutes of Health-funded Penn State General Clinical Research Center.

The investigators found that the maximum tolerated dose of OGF administered intravenously was 250 μg/kg. At 250 μg/kg, two patients experienced mild symptoms of toxicity, the most severe of which was temporary hypotension, or low blood pressure.

In a second part of the study, 10 patients were treated with 250 μg/kg intravenous infusions of OGF, this time delivered over 45 minutes. Because the timing of drug delivery was extended, there were no incidents of toxicity. Six other patients were treated with 50 μg/kg OGF injections twice per day.

Results showed that, unlike the chemotherapeutic agents often used to treat pancreatic cancer, OGF did not cause white blood cell, platelet or iron counts to drop, and did not cause gastrointestinal problems. Nor were there side effects such as hair loss, nausea or loss of appetite.

Quality of life surveys administered before and during the study showed that patients had improved social interaction and alertness behavior, improved sleep and rest, mobility and communication. Pain and depression surveys showed a diminishment in pain scores at certain points during the therapy, and that OGF did not induce depression, but may have actually prevented the development of depression in the terminally-ill patients.

"Although this study was not intended to examine tumor response or survival, our preliminary results showed two patients with spread of the cancer to the liver responded with loss of metastases, and survival was increased from 5.6 months under the typical treatment with gemcitabine, to 9.1 months with OGF," Zagon said. "Some patients survived from 21 to 23 months."

Zagon said preclinical studies of OGF indicate that it may be useful in the treatment of other cancers that rely on OGF for growth such as colon, head and neck, kidney and developing nervous system.

The investigators are currently enrolling patients in a larger, phase II study of OGF for the treatment of pancreatic cancer sponsored by the National Institutes of Health. For more information or to be evaluated for inclusion in the trial, contact Sandra Bingaman, R.N., research study coordinator, at (717) 531-8108.

Co-authors on the study were: Jill P. Smith, M.D., Robert L. Conter, M.D., Sandra I. Bingaman, Harold A. Harvey, M.D., David T. Mauger, Ph.D., Mejdi Ahmad, M.D., Lawrence M. Demers, Ph.D., Wayne B. Stanley, and Patricia J. McLaughlin, Ph.D., Penn State College of Medicine, Penn State Milton S. Hershey Medical Center.

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