Octreotide (Sandostatin), a somatostatin analog, has a wide range of uses in
the management of cancer patients. It is a unique molecule that specifically binds to somatostatin receptor subtype 2. This property of activating the
receptor can result in a multitude of physiologic actions (for example,
inhibition of synthesis and release of peptides in endocrine and neoplastic
cells, antiangiogenesis, antisecretory effect in the gastrointestinal mucosa,
anticholecystokinin activity retarding gallbladder motility, and reduction in
splanchnic blood flow). In addition, in vitro experiments confirm that
octreotide has cytostatic activity against a variety of malignancies. Octreotide
is now widely used in the treatment of hormonal syndromes that result from a
variety of neuroendocrine and endocrine neoplasms. Its dramatic effect in
controlling malignant carcinoid syndrome and hormone-induced diarrhea (for
example, from gastrinoma and VIPoma) has been well documented. However, the
chronic use of octreotide can result in steatorrhea and gallstone formation.
Radiolabeled octreotide has been used successfully for imaging (neuroendocrine,
endocrine, breast, small-cell lung, and prostate cancers) and more recently for
targeted radiotherapy. It is also an effective agent for the control of
therapy-induced diarrhea refractory to oral therapy. Could this molecule have an
expanded role in cancer research? A 2-day meeting of investigators familiar with
octreotide research was held in April 2002 to discuss this question. This was a
frank, interactive forum reviewing new data on octreotide and the long-acting
release (LAR) formulation, octreotide LAR depot, to determine its future in
There were four main areas of discussion: (1) neuroendocrine
neoplasms, (2) therapy-induced diarrhea (chemotherapy and radiotherapy), (3)
review of potential research in pancreatic, hepatocellular, and prostate
cancers, and (4) exploitation of novel properties of this molecule (antiangiogenic
In this supplement, Irvin Modlin and
Lowell Anthony review the
current status of neuroendocrine tumors; both emphasize the emerging role of
radiolabeled octreotide in therapy for these neoplasms. Dr. Anthony discusses
the possibility of additional new targets in the treatment of these
malignancies. He feels that survival time of patients with these indolent
neoplasms can be prolonged substantially, making these neoplasms even more
chronic conditions than they are now. This would be a highly desirable strategy
for future research.
Scott Wadler and Babu Zachariah discuss potential research
avenues with octreotide LAR depot in the field of therapy-induced diarrhea. Dr.
Wadler points out the lack of awareness of diarrhea as a serious toxic effect of
therapy. This lack of awareness is further amplified by the lack of
infrastructure and skills of many practices in the management of diarrhea. He
also characterizes the high-risk patient with "gastrointestinal
syndrome." He states that diarrhea can no longer be treated and dealt with
in isolation. Associated "risk factors" must be considered as well. He
notes the value of octreotide in the treatment of National Cancer Institute
(NCI) Common Toxicity Criteria grade 3 and 4 diarrheas but elaborates on the
emerging role of prophylactic octreotide (particularly the use and research on
octreotide LAR depot).
Dr. Zachariah discusses the serious lack of awareness and
research on radiotherapy-induced diarrhea. He notes that this toxic effect is
very common (up to 40% of patients experience grade 3 or 4 diarrhea) in patients
receiving pelvic chemoradiotherapy. He reports on two small studies that
demonstrated potential benefit of therapy with octreotide but emphasizes and
outlines two cooperative group studies (by the Radiation Therapy Oncology Group
and the North Central Cancer Treatment Group) that would systematically evaluate
the value of prophylactic octreotide LAR depot.
Jordan Berlin, Lewis
Roberts, and Larry Kvols and Viktor Boerlin
discuss various tumor types and potential avenues of research for octreotide.
Dr. Berlin reviews the current status of various therapies in the treatment of
pancreatic carcinoma. He notes that octreotide has limited activity in this
extremely malignant process and is not likely to play a role in its management.
Dr. Roberts discusses data from several published studies and emphasizes the
need for further research to ascertain the role of octreotide LAR depot in the
treatment of advanced hepatocellular carcinoma. Drs. Kvols and Boerlin note that
differentiation of the neuroendocrine neoplastic cell population in prostate
cancer is frequent and has been underestimated. Preliminary data suggest some
biologic activity of octreotide but further research is necessary.
Finally, Eugene Woltering explains the antiangiogenic properties
of octreotide and discusses methods to exploit these properties in future
In summary, the conference proved very productive in reviewing
the current information on octreotide in cancer and therapy-induced
complications. More importantly, we could determine and rank new research
directions. Several potential study designs were reviewed and discussed frankly.
We hope to revisit these and other topics annually.