The hormone somatostatin(Drug information on somatostatin) may be effective in treating some patients with pancreatic cancer, new research suggests. Studies conducted in mice and in laboratory samples found that pancreatic tumors responded to somatostatin only if the tumor cells had receptors for the hormone.
It is not known how many patients might have a form of pancreatic cancer with these receptors, said William Schirmer, coauthor of the study and assistant professor of surgery and a member of Ohio State University's Comprehensive Cancer Center. But, he said, future research should look into the issue.
This is the first study to show a possible role for somatostatin receptors in pancreatic cancer, the fourth leading cause of cancer death in the United States. Only about 2% of patients are alive 5 years after diagnosis, and there are no effective treatments for the disease.
Several small clinical trials at individual medical centers have tested the use of somatostatin to slow or prevent the recurrence of pancreatic cancer following surgery. Those trials, however, have shown that somatostatin does not prolong the lives of patients with pancreatic cancer.
"I'm not surprised by those results," said Schirmer. "Those studies did not look at whether the tumors in those patients showed the presence of somatostatin receptors."
"Our data suggests that there may be a minority of patients who would benefit from somatostatin therapy. But I think these patients are being missed because the trials haven't identified which patients have the receptors." Schirmer and a team of researchers presented their data at the American College of Surgeons meeting in October and at the Association for Academic Surgeons in November.
Presence of Somatostatin Receptors an Important Determinant of Response
It is possible that somatostatin could inhibit tumor growth indirectly. It could inhibit the production of a growth factor or hormone that stimulates tumor growth, for example.
But Schirmer's work suggests that the presence of receptors is the single most important factor in determining whether a tumor responds to treatment with somatostatin, which is often considered an antigrowth hormone.
The researchers studied the effect of somatostatin on human pancreatic cancer cells growing in the laboratory and later in animals. Out of 10 different pancreatic cancer cell lines, only 1 responded to somatostatin. It was also the only cell line with receptors for the hormone.
The researchers then went back and studied each cell line more closely. They have done a detailed characterization of 6 of the 10 cell lines so far.
They looked, for example, at whether somatostatin slowed the growth of the cells growing in culture. They found that while somatostatin had no effect on the cancer cells without receptors, it could slow the growth of cancer cells with receptors by as much as 20%.
The researchers also used the cells to grow tumors in mice. They have transplanted six of the cancer cells into groups of 20 mice, 10 of which were treated with somatostatin. After 36 days, the researchers measured the size of the tumors.
Tumors from mice with somatostatin receptors were half the size of those of the controls (which did not receive somatostatin). In mice with tumors that lacked the receptors, there was no significant difference in tumor size between the somatostatin-treated mice and control animals.
"We're not to the point where we can say that the receptor studies on the human cell lines is going to predict a response," said Schirmer, "but I think we can say that receptor analysis should be considered in future studies to help explain the results of clinical trials using somatostatin for pancreatic cancer."
Clinical Trials Planned
Schirmer notes that if only 5% of people with pancreatic cancer have the receptor, for example, it means that, on average, 80 out of 100 patients in a clinical trial wouldn't respond to somatostatin, "and the treatment will be deemed a failure when looked at statistically," he said.
"But what if the patients with receptors have a good response? We need to be able to sort that out so we can say from the study that, although somatostatin doesn't work in 80% of patients, it does work in those who do have the receptors."
Schirmer is planning a clinical trial at Ohio State that will do just that. The beginning of that trial is months away, however.
The research group is also studying pancreatic tumors removed during surgery for the presence of somatostatin receptors. They are correlating them with scintigraphy scans that use a radioactive form of somatostatin. This could provide a nonsurgical means of determining whether somatostatin receptors are present in a patient.
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