High Dose Somatostatin Analogues in Neuroendocrine Tumors
Status:
Completed
Trial end date:
2008-12-01
Target enrollment:
Participant gender:
Summary
Octreotide (OCT) is a somatostatin analogue (SSA) available in a long-acting formulation,
conventionally administered every 28 days at the maximum dose of 30 mg. Together with
lanreotide, it is considered the therapy of choice in the control of endocrine syndromes
associated with neuroendocrine tumors (NET)s. A complete or partial clinical response to SSA
therapy is generally achieved in at least 50% of the patients with neuroendocrine syndrome.
Many studies reported a clinical response in 70-90% of functioning NETs. In about 36-50% of
the patients with progressive advanced well differentiated NET (WDNET), a stabilization of
disease occurs after treatment with subcutaneous OCT. By developing long-acting slow-release
SSA formulation, long-acting OCT (LAR), lanreotide-SR, lanreotide-Autogel, the patient's
compliance to SSA therapy was improved and escape from treatment, which was common with the
subcutaneous formulation, was avoided. However, rate of objective response was not
significantly improved as compared to short-acting SSA. On the other hand, it has to be
remarked that long-acting SSA are being used in NET patients at doses correspondent to the
low doses of short-acting formulation. The higher commercially available doses of LAR is 30
mg, which is assumed to be comparable to 300 µg of short-acting OCT in the therapy of
acromegaly.
Only one study was designed to investigate the use of high-dose LAR (160 mg every 28 days).
In this study, objective and hormonal responses in patients with progressive metastatic ileal
NET non-responder to standard doses, was significantly elevated. However, this compound has
never been commercialized and, of consequence, this first preliminary observation has not
been confirmed by further studies.
No systematic studies were performed with the commercially available long-acting SSA used in
high-dose treatments. In patients with progressive locally advanced or metastatic NET,
increase of the dose or reduction of the interval between injections is a relatively common
"empirical" clinical practice, but no studies have been performed to evaluate safety and
efficacy of this treatment schedule.
Phase:
Phase 2
Details
Lead Sponsor:
Federico II University
Collaborators:
University Hospital, Udine, Italy University of Genova University of Perugia, Faculty of Medicine, Department of Internal Medicine