Growth factor a new option in pancreatic cancer?

The scientists, from Penn State College of Medicine, have tested opioid growth factor (OGF) in humans for the first time, following up a series of preclinical experiments which suggested that it can slow down the growth of pancreatic tumour cells.

Cancer of the pancreas is the fourth leading cause of cancer death and, because it is usually diagnosed after it has spread to other areas of the body, as many as 98 per cent 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, a team led by Ian Zagon, professor of neural and behavioral sciences, at Penn State, found that OGF is intrinsically involved in the reproduction of some cell types. The growth factor has been more commonly studied for its role in suppressing pain in the nervous system.

Pancreatic cancer cells have OGF receptors that, when bound with the protein, 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.

In the Phase I clinical study, sponsored by the National Institutes of Health, 21 patients with advanced, inoperable, pancreatic cancer were receive OGF either intravenously once per week (at doses of 25mcg/kg to 250mcg/kg), or by self-administered subcutaneous injection (50mcg/kg doses of OGF twice per day).

In the first phase of the study, designed to test the treatment's safety, the investigators found that the maximum tolerated dose of OGF administered intravenously was 250mcg/kg. At this dose, two patients experienced mild symptoms of toxicity, the most severe of which was temporary low blood pressure.

In a second part of the study, 10 patients were treated with 250mcg/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 50mcg/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 behaviour, 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.

Some anticancer effect observed​

"Although this study was not intended to examine tumour 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,"​ said Zagon. And 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. The study appears in appeared in the March 2004 issue of the journal Anti-Cancer Drugs.