Treatment of type I gastric neuroendocrine tumors with somatostatin analogs

Background and Aim: There are limited data on response and long‐term follow‐up of octreotide therapy in type‐I gastric neuroendocrine tumors. The objective of the present study was to assess the response of type‐I gastric neuroendocrine tumors to octreotide‐long acting, repeatable (LAR) therapy and evaluate long‐term follow up of such patients after therapy. Methods: Three patients with documented type‐I gastric neuroendocrine tumors from a tertiary gastroenterology centre were studied. Octreotide‐LAR therapy 20 mg intramuscularly every 28 days was administered for one year. Serum gastrin and chromogranin levels, gastroscopies and biopsies from tumor nodules at 6 months and one year on therapy and every 6 months after completion of drug therapy were taken. Follow‐up after completion of therapy extended for 3 years in two and 2.5 years in one patient. Results: During octreotide therapy there was normalization of serum gastrin levels and serum chromogranin levels. Tumors in all three patients had regressed at 6 months of treatment. Following cessation of therapy, there was progressive rise of serum gastrin to pre‐treatment levels. Serum chromogranin levels remained within normal limits. Gastroscopic and histologic examination of gastric biopsies did not reveal recurrence of tumors in any patients. All patients tolerated therapy well and became asymptomatic soon after drug therapy. Conclusions: Octreotide‐LAR therapy causes regression of type‐I gastric neuroendocrine tumors. After completion of drug therapy there was no recurrence of tumors even with continued hypergastrinemia. Octreotide therapy should be considered as one of the treatment options in such patients.     

The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel

The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.     

Evaluation of IGF-I levels during long-term somatostatin analogs treatment in patients with gastroenteropancreatic endocrine tumors

Previous experiments reported desensitization to SS action in rat anterior pituitary cells and cell lines. The aim of the study was to verify whether the lack of desensitization to SS analogs (SSa) observed in acromegalic patients was also present in subjects with normal hypothalamic-pituitary function. The effect of chronic treatment with octreotide long-acting release (o-LAR, 10-30 mg/28 days) on IGF-I levels was then evaluated in 23 patients with gastroenteropancreatic (GEP) endocrine tumors (8 gastrinomas, 6 carcinoids, and 9 functioning pancreatic tumors). Serum IGF-I, clinical symptoms, plasma chromogranin-A (CgA) and markers of hepatic synthesis were evaluated before and after a short-term period in all the patients (median 4.5 months), after a medium-term period in 12 (median 18 months) and after a long-term follow-up period in 9 of them (median 48 months). Mean IGF-I levels decreased from 17.3+/-7.0 to 12.8+/-6.2 nmol/l in the short-term (p<0.005) being reduced from baseline concentrations in 87% and under the normal range for age in 35% of patients. Afterwards, they always remained stable both in the medium- and long-term periods, still being low in 3/12 and 2/9 patients, respectively. No alterations in biochemical markers of liver function were found either before or during therapy. No correlation between IGF-I levels, CgA concentrations and/or clinical definitive outcome was observed. In conclusion, the study demonstrated that: a) similarly to that observed in acromegalic patients, chronic o-LAR treatment did not induce desensitization of pituitary SS receptors (SSR) in humans with intact hypothalamic-pituitary axis, and b) in patients with GEP endocrine tumors, GH/IGF-I inhibition did not contribute to SSa efficacy.     

Treatment of neuroendocrine tumors with somatostatin analogs

Neuroendocrine tumors constitute a group of hormone producing tumors originating from neuroendocrine cells in different organs. Most tumors have a low proliferation index measured by Ki67 and the progression of the tumor is slow. However, many patients suffer from endocrine symptoms induced by the hormones produced and released by the tumor cells. For some patients these symptoms can be life- threatening as in midgut carcinoid patients suffering from carcinoid crises with extensive flushes and hypotension or in patients with severe diarrhea induced by tumors producing vasointestinal polypeptide. In many other patients the hormone-induced symptoms interfere with the ability to carry out ordinary daily activities. The introduction of somatostatin analogs in the treatment of these hormone related symptoms has made it possible to control most of them and has added significantly to the quality of life for this group of patients. Unfortunately, the clinical inhibitory effect on tumor growth has not been very good with only 5–10% of the patients showing an objective response. However, stabilization of tumor growth may be achieved in a significant number of patients. In the future, the hope is that development of new somatostatin analogs with broader receptor-binding profiles will give us new analogs which are more efficient with regard to their antiproliferative effect. This possibility will be studied in future trials.     

Treatment of malignant endocrine pancreatic tumors with a new long-acting somatostatin analogue, SMS 201-995

Ten patients with malignant endocrine pancreatic tumors were treated with SMS 201-995 at doses of 50 micrograms twice daily, administered subcutaneously. Four out of 10 patients (40%)-1 patient with the Zollinger-Ellison syndrome and 3 of 6 with the watery diarrhea syndrome--responded objectively with more than 50% reduction of peptide levels, with a median duration of 15.5 months. All four patients improved symptomatically, with decreasing dyspeptic symptoms and decreasing diarrhoea. Three additional patients had a clear relief of symptoms without an effect on tumor-secreted peptides. The disease progressed in three patients during treatment. No reduction of tumor mass was seen in any of the patients. The main side effect noted was a slight but maintained increase in fasting blood glucose in four patients. In conclusion, SMS 201-995 had a beneficial effect in more than half of the patients and seems to be a valuable adjunct to other causal therapy in this patient category, especially in acute situations and weak patients because of its very few side effects.     

Long-term safety and efficacy of depot long-acting somatostatin analogs for the treatment of acromegaly

Depot somatostatin analogs are now increasingly being prescribed as adjuvant and primary therapy for the treatment of acromegaly. Previous studies have shown them to be both effective and safe, suppressing GH levels to less than 2 micro g/liter in 50-65% of cases and normalizing serum IGF-I levels in 65%. However, published data on their long-term efficacy and safety is scanty. We analyzed data from 22 patients (16 female and 6 male) treated with Sandostatin LAR or Lanreotide for an average of 41 months (range 12-89). Three patients had previously been treated with surgery, two with radiotherapy, and seven with both. Ten patients had received primary medical therapy. Mean pretreatment GH levels were 13.1 +/- 3.4 micro g/liter, and IGF-I levels were 592.9 +/- 53.9 micro g/liter. Results after 12 months of therapy indicated reduction in GH (3.2 +/- 0.7 micro g/liter; P < 0.0001) and IGF-I (321.9 +/- 33.9 micro g/liter; P < 0.001) concentrations, and this was sustained at latest follow-up. Using GH criteria (serum GH < 2 micro g/liter), 46% of subjects achieved a cure at 12 months, and 36% achieved a cure long-term. Fifty-two percent achieved normal IGF-I values at 12 months, and 67% long-term. Mean fasting and 2-h plasma glucose concentrations were similar at latest follow-up and at 12 months to baseline values. Three patients developed impaired glucose tolerance within 12 months of treatment, one going on to develop frank diabetes mellitus. However, glucose tolerance improved in five patients. Five patients developed gallstones while on treatment. In summary, this study reports the long-term efficacy of the depot somatostatin analogs as either adjuvant or primary therapy. Although overall glucose tolerance did not change, the development of impaired glucose tolerance in three patients at a time when GH levels were not changing highlights the ongoing need to monitor the long-term safety of these preparations.     

The use of a long-acting somatostatin analogue in the treatment of advanced endocrine malignancies with gastrointestinal symptoms

Four patients with advanced endocrine malignancies were treated with a somatostatin analogue (SMS 201-995) for palliation of hormone-induced symptoms during 3-6 months. Two had the carcinoid syndrome (one midgut and one foregut), one had medullary thyroid carcinoma and an ectopic ACTH syndrome, and one patient had a metastatic gastrinoma. The carcinoid patients had excellent symptomatic relief with a low dose of the drug, 50 micrograms subcutaneously twice daily, in one case despite progression of tumour disease and biochemical tumour markers. These findings indicate an action of the drug not only on hormonal release but also at peripheral sites. The patient with medullary thyroid carcinoma had relief of gastrointestinal symptoms when the drug dose was increased (100 micrograms twice daily). The levels of ACTH in peripheral blood were reduced, but not the calcitonin levels. The gastrinoma patient had undergone a major pancreatic resection (Whipple procedure) and was treated with omeprazole. SMS 201-995 reduced the peripheral gastrin levels acutely, but during the treatment fasting gastrin values increased, and the tumour growth progressed. Treatment was stopped owing to elevated fasting glucose level, increased steatorrhoea, and clinical attacks of cholangitis. Special attention is advocated for patients with major pancreatic resection and biliary reconstruction, who may be susceptible to physiological effects of somatostatin (or its analogues)--that is, impaired insulin release and decreased motility.     

Development of resistance to a long-acting somatostatin analogue during treatment of two patients with metastatic endocrine pancreatic tumours

Two patients with metastatic endocrine pancreatic tumours initially responded well to therapy with the long-acting somatostatin analogue SMS 201-995. In the first patient with an insulinoma both the number of hypoglycemic attacks and the increased insulin levels decreased initially, but returned to pretreatment intensity and concentrations within 9 days after the start of therapy with 200-300 micrograms SMS 201-995 daily. After a short interruption, no effect was observed of re-institution of therapy at a dose of 400 micrograms SMS 201-995 daily. In the other patient with a metastatic vipoma both diarrhea, hypokalemia and plasma VIP levels reacted initially well to SMS 201-995 treatment with 300 micrograms per day, but resistance to therapy developed after 2 weeks. An increase in the dose of the analogue to maximally 600 micrograms/day was followed by a transient improvement, but finally both the volume of diarrhea and the levels of vasoactive intestinal polypeptide were higher than those before the start of therapy. Conclusions: Development of resistance to SMS 201-995 both with regard to the clinical effect and to the inhibitory effect on tumour hormone secretion can be expected in some patients with metastatic endocrine pancreatic tumours. On the basis of our clinical observations down-regulation of somatostatin receptors is suggested to be one of the mechanisms of this development.     

Biotherapy of pancreatic neuroendocrine tumors using somatostatin analogs

Basically, pancreatic neuroendocrine tumor (PNET) should be treated surgically; however, in unresectable cases, a treatment that aims to improve the prognosis by inhibiting the growth of the tumor and control the clinical symptoms becomes necessary. In the case of functional tumors, the quality of life of patients is decreased by not only the symptoms with tumor invasion and/or metastasis but also by the symptoms of hormone excess. The efficacy of somatostatin analogs against the latter has been previously reported, and their sustained release formulations have been developed. Somatostatin analogs are recommended to treat the endocrine symptoms of functional PNET; however, in case they can cause hypoglycemia in patients with insulinoma. On the other hand, results from the PROMID study demonstrated a tumor‐stabilizing effect when octreotide LAR (long acting repeatable) was used to treat patients with advanced midgut NET; however, there has been no consensus regarding its antitumor effect for PNET. Additionally, a recent result from the CLARINET study suggests that lanreotide autogel has an antitumor effect against nonfunctional NET including PNET. Further clinical study results are awaited.     

Gastric secretion and hormonal interactions in multiple endocrine neoplasia type I

Results of preparathyroidectomy and postparathyroidectomy studies in a patient with multiple endocrine neoplasia type I and gastrinoma suggest that hyperparathyroidism unmasks occult gastrinoma and related secretory abnormalities. Three of four diagnostic findings were later obscured by parathyroidectomy and normalization of serum calcium concentration. Basal acid output, basal acid output/maximal acid output ratio, and serum gastrin concentration were decreased from values consistent with gastrinoma to normal. The secretin stimulation test, though still positive, was attenuated. These observations suggest that in multiple endocrine neoplasia type I, normal values for serum gastrin concentration, gastric secretion, and secretin stimulation may not exclude gastrinoma. The investigations clarify the interpretation of a voluminous but confusing literature on the interrelationship between hyperparathyroidism and altered gastric function in the presence or absence of Zollinger-Ellison syndrome.     

Novel long-acting somatostatin analog with endocrine selectivity: potent suppression of growth hormone but not of insulin

Somatostatin, also known as somatotropin release-inhibiting factor (SRIF), is a natural cyclic peptide inhibitor of pituitary, pancreatic, and gastrointestinal secretion. Its long-acting analogs are in clinical use for treatment of various endocrine syndromes and gastrointestinal anomalies. These analogs are more potent inhibitors of the endocrine release of GH, glucagon, and insulin than the native SRIF; hence, they do not display considerable physiological selectivity. Our goal was to design effective and physiologically selective SRIF analogs with potential therapeutic value. We employed an integrated approach consisting of screening of backbone cyclic peptide libraries constructed on the basis of molecular modeling of known SRIF agonists and of high throughput receptor binding assays with each of the five cloned human SRIF receptors (hsst1-5). By using this approach, we identified a novel, high affinity, enzymatically stable, and long-acting SRIF analog, PTR-3173, which binds with nanomolar affinity to human SRIF receptors hsst2, hsst4, and hsst5. The hsst5 and the rat sst5 (rsst5) forms have the same nanomolar affinity for this analog. In the human carcinoid-derived cell line BON-1, PTR-3173 inhibits forskolin-stimulated cAMP accumulation as efficiently as the drug octreotide, indicating its agonistic effect in this human cell system. In hormone secretion studies with rats, we found that PTR-3173 is 1000-fold and more than 10,000-fold more potent in inhibiting GH release than glucagon and insulin release, respectively. These results suggest that PTR-3173 is the first highly selective somatostatinergic analog for the in vivo inhibition of GH secretion, with minimal or no effect on glucagon and insulin release, respectively.     

Peptide hormone markers in screening for endocrine tumors in multiple endocrine adenomatosis type I

In three families with the multiple endocrine adenomatosis type I (MEA I) trait, 51 members were investigated by measurement of circulating peptide hormones as tumor markers. Twenty-five of 51 members (49 percent) were considered to be affected by MEA I disorders. The incidence rose with age (75 percent in generation II). Both sexes were affected equally. Hyperparathyroidism was present in 20 of 25 affected members (80 percent), and pituitary tumors (prolactinomas) were found in four of 25 (16 percent). Endocrine pancreatic tumors were found in nine of 25 affected members (36 percent), but when "probable" tumors (seven) are included the frequency rises to 72 percent. Hyperparathyroidism was found in all except one member with proved lesions in other organs. Among patients with proved and possible endocrine pancreatic tumors, elevated serum levels of gastrin and pancreatic polypeptide were frequently found, 78 percent and 67 percent, respectively, and we suggest that serum gastrin and pancreatic polypeptide levels are the most useful screening markers at present for pancreatic lesions in MEA I.     

Metabolic radiotherapy for gastroenteropancreatic endocrine tumors using radiolabeled somatostatin

Surgery is the only curative treatment of gastro-entero-pancreatic endocrine tumors. In inoperable or metastasized forms, therapeutic options are limited. The metabolic or systemic radiotherapy, using radiolabeled somatostatin analogs, constitutes a new therapeutic alternative, currently in development which requires the presence of high affinity somatostatin receptors on tumoral cells. Using (111)In-pentetreotide, the main result is a symptomatic effect. With new somatostatin analogs coupled to B- emitters, such as Octreother or (177)Lu-DOTA-Octreotate, 10 to 30% of objective tumoral responses are observed in progressive patients, unresponsive to conventional treatments. Such results are explained by the high affinity for somatostatin receptors and the large emission diameter of these radiolabeled compounds. Renal toxicity is limited by amino-acid infusion whereas changes in blood count are usually moderate and transient. Multicentric prospective studies are necessary to identify the predictive factors of tumoral response and toxicity. The prospects are related to the development of new radiopharmaceuticals, even more specific of somatostatin receptors sub-types and to the use of other peptide analogues whose applications will overflow the framework of endocrine tumours.     

Octreotide: a long-acting somatostatin analog

One of the exciting recent developments in endocrinology research has been the introduction of the somatostatin analog, octreotide into clinical practice. Octreotide provides a new therapeutic tool for diseases in which somatostatin or somatostatin-like products are secreted abnormally. Unfortunately, early experience was obtained largely with uncontrolled, compassionate drug use. When clinical information regarding octreotide is critically reviewed, evaluation is hampered by the lack of long-term studies with adequate numbers of patients and controls. Nevertheless, the information available does indicate that octreotide is promising in the acute treatment of some of the manifestations of the carcinoid syndrome, including carcinoid crisis. Similarly, octreotide ameliorates symptoms of other gut neuroendocrine tumors, particularly vasoactive intestinal peptide (VIP)-secreting tumors. Octreotide also has potential in the management of growth-hormone-secreting tumors. Long-term treatment with octreotide for these diseases requires more information regarding alterations in disease progression and development of adverse effects including variable effects on blood sugar regulation and steatorrhoea. Octreotide also has been used in nonmalignant gastrointestinal disorders, but larger studies are necessary before recommendations regarding these applications can be made. The cost of octreotide, as may be expected, is high but is justified for patients with the specific indications outlined in this review. These indications may change as understanding of the drug increases. Octreotide offers promise, particularly as acute treatment for the troublesome symptoms of several neuroendocrine disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment

OBJECTIVE: Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty-four active acromegalic patients were studied in order to determine the long-term effects of octreotide-LAR and SR-lanreotide on insulin sensitivity and carbohydrate metabolism. DESIGN: Prospective study. PATIENTS: We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50.7 +/- 12.7 years, body mass index (BMI) 30.1 +/- 4.8 (kg/m2). MEASUREMENTS: All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy. RESULTS: Acromegalic patients showed low M-values in respect to the control group at baseline (P<0.05), followed by a significant improvement after 6 months of therapy (P<0.005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P<0.05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P<0.05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4.7 +/- 0.6% and 5.1 +/- 0.5%, basal and after six months, respectively, P<0.005). CONCLUSION: In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy.     

Comparison between six-year therapy with long-acting somatostatin analogs and successful surgery in acromegaly: effects on cardiovascular risk factors

CONTEXT: The effects of chronic therapy with long-acting somatostatin analogs (SSTa) on metabolic and cardiovascular parameters have been partially elucidated in acromegalic patients. OBJECTIVE: The objective of this study was to compare the long-term effects of SSTa treatment and successful surgery on GH/IGF-I secretion and cardiovascular risk parameters in acromegaly. DESIGN, PATIENTS, AND INTERVENTION: This was a retrospective study of 36 acromegalic patients treated with SSTa and evaluated after a median of 66 months and of 33 sex-, age-, and body mass index-matched cured patients evaluated after a similar period of remission, all from the Institute of Endocrine Sciences (Milan, Italy). MAIN OUTCOME MEASURES: The main outcome measures were fasting and post-oral load glucose homeostasis, hemoglobin A(1c), insulin sensitivity and secretion by several indexes, lipid profile, and blood pressure. RESULTS: Fasting and areas under the glucose response curve rose in patients controlled (n = 29) and not controlled (n = 7) by SSTa, becoming higher than those in cured subjects. A 1% hemoglobin A(1c) increase was observed in all nondiabetic SSTa patients, but not in cured subjects. Basal insulin secretion and resistance, evaluated by homeostasis model assessment, decreased in all SSTa patients, whereas oral glucose tolerance test-derived insulin secretion and resistance, evaluated by insulinogenic index and oral glucose tolerance test-derived insulin secretion, improved only in SSTa-treated controlled patients. Triglycerides did not change during SSTa, whereas high-density lipoprotein cholesterol increased in SSTa-treated controlled patients. At the last visit, the contemporary presence of at least three cardiovascular risk factors was more frequent in patients treated with SSTa than in cured subjects. CONCLUSIONS: SSTa therapy induces long-lasting disease control and improvement of insulin sensitivity and high-density lipoprotein cholesterol levels in responsive patients. The progressive glucose homeostasis alterations, observed independently from the degree of cure, suggest the need for glucose homeostasis and peripheral vascular complications monitoring during chronic SSTa treatment.     

The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors

OBJECTIVE: Somatostatin analogs are the first-line drugs for controlling hormone-mediated symptoms of carcinoid tumors. Prospective and retrospective studies have suggested that somatostatin analogs also have antiproliferative activity. The octapeptide lanreotide is available in sustained-release form, obviating the need for daily injections. METHODS: A total of 46 patients were enrolled in this open, prospective, phase II trial. They received lanreotide 30 mg i.m. every 14 days for 6 months when they had symptomatic carcinoid tumors, and lanreotide 30 mg i.m. every 10 days if they had nonsymptomatic tumors. Nonsymptomatic tumors were progressive before the start of the study. Tumor size was assessed every 3 months by means of computed tomography. The assessment was centralized and was made by an external panel. RESULTS: In all, 30 patients had symptomatic neuroendocrine tumors and 16 had asymptomatic neuroendocrine tumors. Five patients in the group with symptomatic tumors and two in the group with nonsymptomatic tumors were considered not to be evaluable. The mean duration of treatment was 12 months in the group with symptomatic tumors and 13 months in the other group. Among the 39 evaluable patients, two objective responses were obtained, giving an objective response rate of 5% (one in the group with symptomatic tumors and one in the other group). Nineteen patients had no significant increase in their tumor size for a mean of 9.5 months. CONCLUSIONS: Lanreotide is safe and well tolerated in patients with carcinoid tumors. It seems to have both symptomatic and antitumoral effects in this setting.     

Clinical review 23: The use of the long-acting somatostatin analog octreotide in the treatment of gut neuroendocrine tumors.

The SRIF analog octreotide (SMS 201-995) has been in clinical use for over 6 yr in the treatment of acromegaly and metastatic endocrine pancreatic and carcinoid tumors. The use of the analog in the treatment of acromegaly and TSH-secreting tumors is beyond the scope of this clinical review. Patient acceptance of the analog, given chronically by the sc route, has been excellent and side effects have been few with the exception of the development of gallstones. In endocrine pancreatic and carcinoid tumors the hypersecretion of hormones such as VIP, glucagon, and gastrin and the secretory products of carcinoid tumors (e.g. 5-hydroxytryptamine and tachykinins) and their clinical effects may be successfully blocked. This allows excellent palliation of such tumors and often enables the patients to return home and lead normal social lives. Initial hopes that long-term octreotide therapy would be an effective antitumor drug, reducing tumor growth, based on experimental animal models and human tumor cell lines, have not been born out in clinical practice. A reduction in gut tumor bulk due to octreotide, rarely or never occurs as a sustained phenomenon. Eventually a decrease in, and finally an absence of, clinical effectiveness occurs despite the reintroduction of other treatment modalities.