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Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial.

BACKGROUND & AIMS: The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure (progression, death, stop of study treatment) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut (mainly pancreatic) and midgut tumors. METHODS: One hundred nine of 125 registered patients were randomized starting in January 1995, and 105 patients (51 monotherapy, 54 combination treatment) were finally analyzed in March 2000. Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging. Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not randomized because of stable disease. RESULTS: Partial tumor regression occurred in 2.9%, 1.9%, and 5.7% and stabilization of tumor growth in 44.8%, 27.6%, and 15.2% at 3, 6, and 12 months, respectively, with no significant differences between both treatment arms. In March 2000, 9.5% of patients were in treatment. Time to treatment failure and long-term survival did not differ significantly between the 2 groups, with a median survival of 32 and 54 months for the octreotide and the combination groups, respectively. Survival was longer in patients not randomized because of stable disease (median, 68 months) and in those with low nuclear Ki-67. A trend toward longer survival was shown for patients with slow spontaneous tumor growth before randomization. Patients responding to treatment lived longer than unresponsive patients. CONCLUSIONS: Combination treatment was not superior to monotherapy concerning progression-free and long-term survival. Patients responding to treatment and those with slow spontaneous tumor growth had a survival advantage.

Adolescent↗

Octreotide scintigraphy and Chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer.

In this pilot study, the predictive value of Octreotide scintigraphy (Octreoscan) and/or Chromogranin-A (CgA) was investigated in patients with hormone-refractory prostate cancer treated with Octreotide acetate. In total, 20 patients with progressive disease and bone metastases entered the trial. At baseline Octreoscan, CgA, PSA, alkaline phosphates (ALP) and two self-administered questionnaires (EORTC QLQ C-30 (v3) and brief pain index) were performed and a diary of the pharmaceutical was started. The treatment consisted of Octreotide (Sandostatin LAR) acetate 30 mg intramuscular injection every month. The blood samples and questionnaires were repeated every month until 3 months. Clinical responder was defined as a patient with increased global health score more than 10 units and stable or decreased pain score without an increase in analgesic. In all, 17 patients were treated per protocol, and four were assessed as clinical responders. Six patients developed a reduction in ALP (median -26%, range -5 to -78%). All patients increased in PSA. At baseline, three patients had a negative Octreoscan and the patients with positive lesions, demonstrated uptake of low intensity. At baseline the CgA was elevated above the normal range in 15 of the patients, and during treatment five patients decreased their CgA to the normal range. Neither baseline Octreoscan nor CgA could identify the clinical reponders. A minority of patients improves their health-related quality of life. The decrease and normalization of CgA levels in five patients during therapy indicates therapeutic activity but Octreoscan and CgA could not identify clinical responders.

Aged↗

Effects of treatment with octreotide in acromegalic patients--a multicenter Italian study. Italian Multicenter Octreotide Study Group.

Treatment of acromegaly is effective in reversing the reduced life-span of patients only when serum growth hormone (GH) concentrations are lowered to less than 2.5 micrograms/l. Usual treatments achieve this goal in no more than 50-60% of patients. The effects of octreotide were studied in a prospective, open label study with 68 acromegalic patients enrolled in 10 Italian centers. Octreotide was administered sc at a dose of 100 micrograms t.i.d. for 1 year. After 3 months of therapy, octreotide was effective in decreasing serum GH levels below 2.5 micrograms/l in 16 out of 64 acromegalic patients (25%). Fifteen of them had pretreatment GH levels below 25 micrograms/l. Insulin-like growth factor I (IGF-I) levels normalized in about 40% of patients. No further GH reduction was observed after 1 year of treatment. The presence of abnormal GH responses to thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone was reduced from 54 to 24% and from 16 to 12%, respectively. Tumor shrinkage was observed in 50% of 26 non-irradiated patients after 12 months of treatment. Both basal and TRH-stimulated serum prolactin levels significantly decreased in the 11 hyperprolactinemic patients. Although serum thyrotropin, free triiodothyronine and free thyroxine concentrations were not modified, a significant reduction of thyrotropin response to TRH was observed in the 9th month of therapy. In non-diabetic patients, an increase of mean blood glucose levels without modifications of fasting morning concentrations was found. About one-quarter of the patients with overt diabetes mellitus had an impairment of their metabolic control. Main clinical symptoms of acromegaly improved in 70-80% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

[Acute test with subcutaneous octreotide as a predictor of the response to treatment with octreotide LAR].

Somatostatin analogues are frequently used to treat acromegaly. To determine the value of the acute test (AT) with subcutaneous (SC) octreotide as a predictor of the response to treatment with octreotide LAR, we analyzed data from 20 patients. For the AT, blood was drawn before and two hours after the SC administration of octreotide for measuring GH. GH levels before and after the AT were 21.9 ng/mL (2.3-143.4) and 3.1 ng/mL (0.3-61.3), respectively. Control of the disease was defined as: GH< 2.5 ng/mL and normal IGF-I anytime during treatment. Sensitivity, specificity, positive and negative predictive values of the AT were 0.9, 0.6, 0.69 and 0.86 for a reduction of 75% of the GH on the test. From our sample we conclude that a 75% reduction of the GH levels during the acute test was able to discriminate patients with a higher or lower chance of responding to treatment.

Acromegaly↗

Iodine-123-Tyr-3-octreotide uptake in pancreatic endocrine tumors and in carcinoids in relation to hormonal inhibition by octreotide.

UNLABELLED: Uptake of 123I-Tyr-3-octreotide (TOCT) by hormone-secreting abdominal tumors was studied to compare scintigraphic observations with the reduction in hormone levels brought about by a brief therapeutic test. METHODS: A prospective study was conducted on 17 patients, totalizing 46 proven lesions, with endocrine tumors of the pancreas (10 patients, 20 lesions) and/or carcinoid metastases (8 patients, 26 lesions). Tumor hormonal hypersecretion was inhibited by octreotide. RESULTS: There was good agreement between the results of these examinations. CONCLUSIONS: The detection of abdominal tumors using this radiotracer is strongly related to its functional characteristics. Variations in the scintigraphic and test results according to different tumor types were in agreement with published data on the density of somatostatin receptors measured by in vitro studies or scintigraphy and by the therapeutic effects of octreotide.

Adult↗

Non-islet cell tumour-associated hypoglycaemia: 111In-octreotide imaging and efficacy of octreotide, growth hormone and glucocorticosteroids.

A patient presented with frequent episodes of spontaneous hypoglycaemia due to a solitary fibrous tumour of pleural origin, secreting incompletely processed pro-insulin-like growth factor II (big IGF-II). Somatostatin receptors were demonstrated in the tumour by 111 inlabelled octreotide scintigraphy, but despite maximal doses of octreotide, there was no suppression of big IGF-II secretion and the hypoglycaemia persisted. The combination of GH and glucocorticoid therapy abolished the hypoglycaemia.

Aged↗

Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake.

UNLABELLED: Scintigraphy with [111In-diethylenetriamine pentaacetic acid0-D-Phe1]-octreotide (DTPAOC) is used to demonstrate neuroendocrine and other somatostatin-receptor-positive tumors. Despite encouraging results, this 111In-labeled compound is not well suited for peptide-receptor-mediated radiotherapy of somatostatin-receptor-positive tumors. Another somatostatin analog, [1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid0, D-Phe1, Tyr3]-octreotide (DOTATOC), can be labeled with the beta-emitter 90Y in a stable manner. METHODS: We compared the distribution, kinetics and dosimetry of 111In-DTPAOC and 111In-DOTATOC in eight patients to predict the outcomes of these parameters in patients who will be treated with 90Y-DOTATOC. RESULTS: Serum radioactivity levels for the radiopharmaceuticals did not differ significantly 2-24 h after injection (P>0.05). Up to 2 h postinjection they were slightly, but significantly, lower after administration of 111In-DOTATOC (P < 0.01 at most time points). The percentage of peptide-bound radioactivity in serum did not differ after administration of either compound. Urinary excretion was significantly lower after administration of 111In-DOTATOC (P < 0.01). The visualization of known somatostatin-receptor-positive organs and tumors was clearer after administration of 111In-DOTATOC than after administration of 111In-DTPAOC. This was confirmed by significantly higher calculated uptakes in the pituitary gland and spleen. The uptake in the tumor sites did not differ significantly (P > 0.05), although in three of the four patients in whom tumor uptake could be calculated, it was higher after administration of 111In-DOTATOC. CONCLUSION: The distribution and excretion pattern of 111In-DOTATOC resembles that of 111In-DTPAOC, and the uptake in somatostatin-receptor-positive organs and most tumors is higher for 111In-DOTATOC. If 90Y-DOTATOC shows an uptake pattern similar to 111In-DOTATOC, it is a promising radiopharmaceutical for peptide-receptor-mediated radiotherapy in patients with somatostatin-receptor-positive tumors.

Adult↗

[123I]Mtr-TOCA, a radioiodinated and carbohydrated analogue of octreotide: scintigraphic comparison with [111In]octreotide.

PURPOSE: Scintigraphy with maltotriose-[123I]Tyr3-octreotate ([123I]Mtr-TOCA) is compared with [111In]DTPA-Phe1-octreotide ([111In]OC) to assess the differences in pharmacokinetics and imaging properties as well as to estimate the therapeutic potential of the corresponding [131I]Mtr-TOCA. METHODS: Six patients with somatostatin receptor (sstr)-positive tumours were assessed using a dual-head gamma camera. After injection of 137 +/- 28 MBq [123I]Mtr-TOCA, dynamic data acquisition of the upper abdomen (30 min) was performed followed by whole-body scans at 0.5 h, 1 h, 3 h and 20 h as well as by SPECT imaging (tumour) at 2 h. [111In]OC scintigraphy was performed by acquiring whole-body scans (4 h, 24 h) and SPECT (24 h). Using a region of interest (ROI) method, tissue and tumour bound activity was assessed and dosimetry performed. RESULTS: [123I]Mtr-TOCA shows rapid tumour uptake. Up to 4 h, tumour/organ (tu/org) ratios are stable and generally higher than with [111In]OC. From 3 h to 20 h, tu/org ratios increase for spleen, remain stable for liver and decrease significantly for all other tissues. In contrast, with [111In]OC, tu/org ratios decrease slightly between 4 h and 24 h for liver, spleen and kidney and increase for all other tissues. On [123I]Mtr-TOCA scintigraphy, a total of 27 lesions are detected, whereas 33 lesions are detected on [111In]OC scintigraphy (p=0.50). Effective patient absorbed dose is 1.9 +/- 0.9 mSv per 100 MBq [123I]Mtr-TOCA. CONCLUSION: Compared with [111In]OC, [123I]Mtr-TOCA enables faster imaging of sstr-positive tumours with a lower radiation burden to the patient. [123I]Mtr-TOCA and [111In]OC allow for tumour imaging with almost identical contrast and diagnostic yield. As regards peptide receptor radionuclide therapy, radioiodinated Mtr-TOCA is hampered by limited intratumoural activity retention

Humans↗

The effect of sequential administration of octreotide alone and octreotide/growth hormone simultaneously on buserelin stimulated ovarian steroid secretion in women with polycystic ovary syndrome.

OBJECTIVE: GH increases oestradiol secretion and promotes oocyte development in women with polycystic ovary syndrome (PCOS). However, there are no data on ovarian androgen production after GH treatment. We have therefore assessed the effect of sequential treatment with a long-acting somatostatin analogue (octreotide) alone and octreotide/GH simultaneously on ovarian steroid levels in PCOS and non-PCOS normal women. PATIENTS: Twenty-six PCOS and 12 non-PCOS women, aged 18-35 years, were studied. Ten of the PCOS and six of the non-PCOS women received sequential treatment with octreotide alone and followed by octreotide + GH together, while another eight PCOS and six non-PCOS women received saline instead of octreotide-octreotide + GH. The remaining eight PCOS women received GH alone. DESIGN: The octreotide-octreotide + GH and saline studies lasted 12 days, the GH alone 7 days. Octreotide (100 micrograms, s.c., t.d.s.) was given from the 2nd to the 10th and octreotide + GH (4 IU, s.c. at 2300h) from the 7th to the 10th day of the study. The GH alone treatment was given from the 2nd to the 5th day. On the 1st day, two tests were performed: (1) an oral glucose tolerance test (OGTT, 75 g, orally) at 0830h and (2) a buserelin (long-acting GnRH agonist) test (100 micrograms, s.c.) at the end of the OGTT. Both tests were repeated on the 6th and 11th days in the octreotide-octreotide + GH or on the 6th day only in the GH alone study. MEASUREMENTS: Blood glucose, insulin (IRI), C-peptide and IGF-I (at time 0 only) were measured before glucose administration and at 30-minute intervals for 3 hours and LH, FSH, delta 4-androstenedione (delta 4A), testosterone (TT), free testosterone (FT) and oestradiol (E2) before buserelin and at 1,2,6,10,14 and 18 hours. RESULTS: Octreotide alone significantly reduced the basal IGF-I stimulated LH and both basal and stimulated IRI, delta 4A, TT, FT and E2 levels in all PCOS women tested. Both octreotide + GH and GH alone increased significantly the basal IGF-I and both basal and stimulated IRI and E2 levels in all PCOS women, while the basal and stimulated LH, delta 4A, TT and FT levels were completely unaffected. In contrast, octreotide-octreotide + GH treatment did not modify either basal or stimulated gonadotrophin or ovarian steroid levels in non-PCOS women. No changes in either basal or stimulated hormone levels were observed in those PCOS women who received saline. Although both basal and stimulated levels of all ovarian androgens were significantly reduced by octreotide-octreotide + GH treatment in PCOS women, they still remained significantly higher than in the non-PCOS women. CONCLUSIONS: The data show that (1) octreotide is a potent inhibitor of ovarian steroid secretion, (2) GH increases oestradiol secretion, possibly by stimulating ovarian aromatase activity, and (3) the combined treatment with octreotide and GH significantly improves ovarlan function in women with PCOS and may thus have important clinical implications for the management of infertile women with this syndrome.

Adolescent↗

Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension.

BACKGROUND & AIMS: Octreotide has been suggested for the treatment of variceal bleeding, but detailed dose-finding studies are not available. We performed a dose-finding study investigating the hemodynamic effects of several forms of intravenous octreotide administration. METHODS: Splanchnic hemodynamics and plasma glucagon levels were measured in 68 cirrhotics in baseline conditions and (1) after a double-blind intravenous injection of octreotide (50 microg [n = 9] or 500 microg [n = 8]) or placebo (n = 7); (2) after a 50-microg octreotide bolus followed by continuous infusion of 50 microg/h (n = 8), 250 microg/h (n = 8), or placebo (n = 6); (3) after repeated 50-microg injections of octreotide (n = 9) or placebo (n = 6) after an initial bolus (50 microg octreotide); and (4) after a placebo bolus and continuous octreotide infusion (50 microg/h; n = 7). RESULTS: Placebo caused no significant changes. Octreotide caused a marked and transient decrease in portal pressure and azygos blood flow and an increase in mean arterial pressure. These effects lasted only 5 minutes despite addition of continuous octreotide infusions. Repeated octreotide injections had shorter, less marked effects than the first bolus. A continuous octreotide infusion did not decrease portal pressure. Glucagon levels were markedly reduced by octreotide, but gradually returned to baseline despite continuous infusions or repeated injections of octreotide. CONCLUSIONS: Octreotide injection caused marked but transient reductions in portal pressure and azygos blood flow. Adding a continuous octreotide infusion neither maintained nor prolonged its effects. Repeated boluses caused significant tachyphylaxis. This rapid desensitization to the effects of octreotide may explain the divergent effects achieved with octreotide infusions in acute variceal bleeding.

Adult↗