High Dose Somatostatin Analogues in Neuroendocrine Tumors
Condition: Respiratory Tract Neoplasms; Thymic Neoplasms; Pancreatic Neoplasms; Gastrointestinal Neoplasms; Multiple Endocrine Neoplasia
MeSH terms: Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Multiple Endocrine Neoplasia; Respiratory Tract Neoplasms; Thymus Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      The patient population will include the patients with a histologically documented diagnosis
      of WDNET, defined according to the last WHO Classification criteria for NET of
      gastro-entero-pancreatic, bronchial, thymic or other origin; and showing tumor progression
      under a standard dose treatment with LAR (30 mg every 28 days) for at least 6 months.
      Progressive disease will be defined as increased tumor size according to RECIST definitions.
    

Intervention name(s): Octreotide-LAR
Intervention type(s): Drug
Intervention description(s): Octreotide-LAR 30 mg administered every 21 days until progression
Other intervention name(s): Sandostatin-LAR; Longastatina-LAR
Intervention MeSH terms: Octreotide
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: neuroendocrine tumors; octreotide; somatostatin analogues