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E. P. Krenning - One of the best experts on this subject based on the ideXlab platform.
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gene transcript analysis blood values correlate with 68ga dota Somatostatin Analog ssa pet ct imaging in neuroendocrine tumors and can define disease status
European Journal of Nuclear Medicine and Molecular Imaging, 2015Co-Authors: Lisa Bodei, E. P. Krenning, Dik J Kwekkeboom, M Kidd, Irvin M Modlin, Vikas Prasad, Stefano Severi, Valentina Ambrosini, Richard A Baum, Giovanni PaganelliAbstract:Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between 68Ga-Somatostatin Analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. We utilized two independent patient groups with positive 68Ga-SSA PET: data set 1 (68Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 (68Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUVmax), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. SUVmax measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ2 = 20.1, p 95 % concordance and significantly correlated with SUVmax (R 2 = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and Somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUVmax. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUVmax [ROC-derived AUC (R 2 = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters was evident. 68Ga-SSA PET imaging parameters (SUVmax) correlated with a circulating NET transcript signature. Disease status could be predicted by an elevated quotient of gene expression (MORF4L2) and SUVmax. These observations provide the basis for further exploration of strategies that combine imaging parameters and disease-specific molecular data for the improvement of NET management.
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treatment with the radiolabeled Somatostatin Analog 177lu dota0 tyr3 octreotate toxicity efficacy and survival
Journal of Clinical Oncology, 2008Co-Authors: Dik J Kwekkeboom, Richard A Feelders, Pete P M Kooij, Woute W De Herde, Caspe H J Van Eijck, Oe L Kam, Martij Van Esse, Maarte O Van Ake, E. P. KrenningAbstract:Purpose Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled Somatostatin Analog [177Lu-DOTA0,Tyr3]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients and Methods Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Results Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Compl...
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radiolabeled Somatostatin Analog 177lu dota0 tyr3 octreotate in patients with endocrine gastroenteropancreatic tumors
Journal of Clinical Oncology, 2005Co-Authors: Dik J Kwekkeboom, Richard A Feelders, Jaap J M Teunisse, Willem H Akke, Pete P M Kooij, Woute W De Herde, Caspe H J Van Eijck, Janpaul Esse, Oe L Kam, E. P. KrenningAbstract:Purpose There are few treatment options for patients with metastasized or inoperable endocrine gastroenteropancreatic (GEP) tumors. Chemotherapy can be effective, but the response is usually less than 1 year. Here, we present the results of treatment with a radiolabeled Somatostatin Analog, [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Patients and Methods One hundred thirty-one patients with Somatostatin receptor-positive tumors were treated with up to a cumulative dose of 600 to 800 mCi (22.2 to 29.6 GBq) of 177Lu-octreotate. Results One patient developed renal insufficiency, and another patient developed hepatorenal syndrome. Creatinine clearance did not change significantly in the other patients. WHO hematologic toxicity grade 3 or 4 occurred after less than 2% of the administrations. We observed complete remission in three patients (2%), partial remission in 32 patients (26%), minor response (tumor diameter decrease of 25% to 50%) in 24 patients (19%), stable disease (SD) in 44 patients (35%), and...
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procedure guideline for Somatostatin receptor scintigraphy with 111in pentetreotide
The Journal of Nuclear Medicine, 2001Co-Authors: Helena Balon, E. P. Krenning, Stanley J Goldsmith, Barry A Siegel, Edward B Silberstein, Otto Lang, Kevin J DonohoeAbstract:The purpose of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of Somatostatin receptor scintigraphy with 111In-pentetreotide. 111In-pentetreotide is a [111In-DTPA-d-Phe-] conjugate of octreotide, a Somatostatin Analog
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radioiodinated Somatostatin Analog scintigraphy in small cell lung cancer
The Journal of Nuclear Medicine, 1991Co-Authors: D J Kwekkeboom, E. P. Krenning, Willem H Bakker, You H Oei, Ted A W Splinter, Siang G Kho, Steven W. J. LambertsAbstract:Somatostatin receptors have been characterized on biopsy specimens from small-cell lung carcinoma (SCLC) and on cultured human SCLC cells. We recently described the in vivo visualization of various Somatostatin receptor-positive tumors, such as carcinoids and endocrine pancreatic tumors, after injection of 123I-Tyr-3-octreotide, a radiolabeled Somatostatin Analog. In the present study, this imaging procedure using 123I-Tyr-3-octreotide is reported in 11 patients with lung tumors. In five of eight patients with SCLC (63%), we were able to demonstrate tumor deposits using 123I-Tyr-3-octreotide scintigraphy. Unexpected metastases were found in two patients. In one of three patients with SCLC in whom tumor was not visualized, nonvisualization may have been caused by tumor necrosis and recent radiotherapy. In one of two patients with malignant small-cell tumors as described by Askin, the neoplasm was visualized. Like SCLC, these tumors are thought to derive from neuroendocrine cells. In one patient, a squamous-cell carcinoma and a bronchial adenoma were not visualized. We conclude that in the majority of patients with SCLC, the tumor and its metastases can be visualized using 123I-Tyr-3-octreotide scintigraphy. However, the value of this new technique in terms of specificity and sensitivity requires further studies in a larger group of patients.
Dik J Kwekkeboom - One of the best experts on this subject based on the ideXlab platform.
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gene transcript analysis blood values correlate with 68ga dota Somatostatin Analog ssa pet ct imaging in neuroendocrine tumors and can define disease status
European Journal of Nuclear Medicine and Molecular Imaging, 2015Co-Authors: Lisa Bodei, E. P. Krenning, Dik J Kwekkeboom, M Kidd, Irvin M Modlin, Vikas Prasad, Stefano Severi, Valentina Ambrosini, Richard A Baum, Giovanni PaganelliAbstract:Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between 68Ga-Somatostatin Analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. We utilized two independent patient groups with positive 68Ga-SSA PET: data set 1 (68Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 (68Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUVmax), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. SUVmax measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ2 = 20.1, p 95 % concordance and significantly correlated with SUVmax (R 2 = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and Somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUVmax. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUVmax [ROC-derived AUC (R 2 = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters was evident. 68Ga-SSA PET imaging parameters (SUVmax) correlated with a circulating NET transcript signature. Disease status could be predicted by an elevated quotient of gene expression (MORF4L2) and SUVmax. These observations provide the basis for further exploration of strategies that combine imaging parameters and disease-specific molecular data for the improvement of NET management.
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treatment with the radiolabeled Somatostatin Analog 177lu dota0 tyr3 octreotate toxicity efficacy and survival
Journal of Clinical Oncology, 2008Co-Authors: Dik J Kwekkeboom, Richard A Feelders, Pete P M Kooij, Woute W De Herde, Caspe H J Van Eijck, Oe L Kam, Martij Van Esse, Maarte O Van Ake, E. P. KrenningAbstract:Purpose Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled Somatostatin Analog [177Lu-DOTA0,Tyr3]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients and Methods Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Results Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Compl...
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radiolabeled Somatostatin Analog 177lu dota0 tyr3 octreotate in patients with endocrine gastroenteropancreatic tumors
Journal of Clinical Oncology, 2005Co-Authors: Dik J Kwekkeboom, Richard A Feelders, Jaap J M Teunisse, Willem H Akke, Pete P M Kooij, Woute W De Herde, Caspe H J Van Eijck, Janpaul Esse, Oe L Kam, E. P. KrenningAbstract:Purpose There are few treatment options for patients with metastasized or inoperable endocrine gastroenteropancreatic (GEP) tumors. Chemotherapy can be effective, but the response is usually less than 1 year. Here, we present the results of treatment with a radiolabeled Somatostatin Analog, [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Patients and Methods One hundred thirty-one patients with Somatostatin receptor-positive tumors were treated with up to a cumulative dose of 600 to 800 mCi (22.2 to 29.6 GBq) of 177Lu-octreotate. Results One patient developed renal insufficiency, and another patient developed hepatorenal syndrome. Creatinine clearance did not change significantly in the other patients. WHO hematologic toxicity grade 3 or 4 occurred after less than 2% of the administrations. We observed complete remission in three patients (2%), partial remission in 32 patients (26%), minor response (tumor diameter decrease of 25% to 50%) in 24 patients (19%), stable disease (SD) in 44 patients (35%), and...
Kjell Oberg - One of the best experts on this subject based on the ideXlab platform.
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37lba telotristat etiprate is effective in treating patients with carcinoid syndrome that is inadequately controlled by Somatostatin Analog therapy the phase 3 telestar clinical trial
European Journal of Cancer, 2015Co-Authors: Matthew H Kulke, Dieter Horsch, Martyn Caplin, Lowell B Anthony, Emily K Bergsland, Kjell Oberg, Staffan Welin, Richard R P Warner, Catherine Lombardbohas, Pamela L KunzAbstract:Telotristat etiprate is effective in treating patients with carcinoid syndrome that is inadequately controlled by Somatostatin Analog therapy (the phase 3 TELESTAR clinical trial)
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37lba telotristat etiprate is effective in treating patients with carcinoid syndrome that is inadequately controlled by Somatostatin Analog therapy the phase 3 telestar clinical trial
European Journal of Cancer, 2015Co-Authors: Matthew H Kulke, Dieter Horsch, Martyn Caplin, Emily K Bergsland, Kjell Oberg, Staffan Welin, Richard R P Warner, Catherine Lombardbohas, Lowell Anthony, P KunzAbstract:Telotristat etiprate is effective in treating patients with carcinoid syndrome that is inadequately controlled by Somatostatin Analog therapy (the phase 3 TELESTAR clinical trial)
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Somatostatin Analog octreotide lar in gastro entero pancreatic tumors
Expert Review of Anticancer Therapy, 2009Co-Authors: Kjell ObergAbstract:Neuroendocrine tumors (NETs) are considered to be rare but, during the last two decades, their incidence and prevalence has considerably increased in gastro-entero-pancreatic (GEP) NETs. Most GEP-NETs express Somatostatin receptors, which could be targets for treatment. The development of Somatostatin Analogs for treatment of functioning NETs was a revolution in the treatment of these patients and is still a cornerstone for managing hormone-related clinical symptoms. Furthermore, Somatostatin Analogs have also demonstrated an anti-tumor effect, with stabilization of tumor growth over long periods of time. The development of a long-acting formulation of octreotide long-acting release (LAR) significantly improved the quality of life for patients with functioning NETs in terms of necessitating only monthly injections. The side effects are few and easily manageable. In the future, Somatostatin Analogs will continue to be a major treatment option for functioning NETs, but will be combined with other biologicals, such as a-interferons, mTOR inhibitors and VEGF inhibitors. A new multireceptor Somatostatin Analog, SOM230 (pasireotide), as well as chimeric molecules, such as dopastatin (a combination of a Somatostatin Analogue plus a dopamine agonist), will come into the clinical management of GEP-NETs.
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interferon α and Somatostatin Analog in patients with gastroenteropancreatic neuroendocrine carcinoma single agent or combination
Annals of Oncology, 2007Co-Authors: Nicola Fazio, F De Braud, Delle G Fave, Kjell ObergAbstract:In most cases gastro-enteropancreatic neuroendocrine tumors grow slowly. Interferon-alpha and Somatostatin Analogs have shown symptomatic, biochemical, and, in a minority of cases, antiproliferative activity. Generally, they are proposed as single-agent therapy. However, based on in vitro and in vivo evidence, the combined use of these drugs was proposed in several non-randomized trials, indicating that there is an additive effect of the combination. Nevertheless, the three randomized trials published so far did not show a statistically significant survival benefit for the combination compared to the same agents alone, even though an advantage for the combination came out in all three studies. On the other hand, data from non-randomized trials would justify the sequential use of the two drugs or the combination after progression on single agent therapy. Therefore, at present the up-front combined use of interferon-alpha and Somatostatin Analog is not justified, whereas it could be indicated after progression to single-agent therapy. Further larger, international, prospective, randomized, multicentric clinical trials studying homogeneous populations would be necessary to give a final answer, but the rarity and heterogeneity of this malignancy does not assure that it will be possible.
Richard A Feelders - One of the best experts on this subject based on the ideXlab platform.
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quality of life in acromegalic patients during long term Somatostatin Analog treatment with and without pegvisomant
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: Sebastian J C M M Neggers, Wouter W De Herder, Richard A Feelders, M O Van Aken, Joseph A M J L Janssen, X Badia, Susan M Webb, Aartjan Van Der LelyAbstract:Objective: The objective of the study was to assess whether weekly administration of 40 mg pegvisomant (PEG-V) improves quality of life (QoL) and metabolic parameters in acromegalic patients with normal age-adjusted IGF-I concentrations during long-acting Somatostatin Analog (SSA) treatment. Design: This was a prospective, investigator-initiated, double blind, placebo-controlled, crossover study. Twenty acromegalic subjects received either PEG-V or placebo for two consecutive treatment periods of 16 wk, separated by a washout period of 4 wk. Efficacy was assessed as change between baseline and end of each treatment period. QoL was assessed by the Acromegaly Quality of Life Questionnaire (AcroQoL) and the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ). Results: The AcroQoL (P 0.008) and AcroQoL physical (P 0.002) improved significantly after PEG-V was added. The addition of PEG-V also significantly improved the PASQ (P 0.038) and the single PASQ questions, perspiration (P 0.024), soft tissue swelling (P 0.036), and overall health status(P0.035).NosignificantchangeinZ-scoreofIGF-I(P0.34)wasobservedduringaddition of PEG-V. Transient liver enzyme elevations were observed in five subjects (25%). Conclusion: Improvement in quality of life was observed without significant change in IGF-I after the addition of 40 mg pegvisomant weekly to monthly SSA therapy in acromegalic patients who had normalized IGF-I on SSA monotherapy. These data question the current recommendations in how to assess disease activity in acromegaly. Moreover, the findings question the validity of the current approach of medical treatment in which pegvisomant is used only when SSA therapy has failed to normalize IGF-I. (J Clin Endocrinol Metab 93: 3853–3859, 2008)
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treatment with the radiolabeled Somatostatin Analog 177lu dota0 tyr3 octreotate toxicity efficacy and survival
Journal of Clinical Oncology, 2008Co-Authors: Dik J Kwekkeboom, Richard A Feelders, Pete P M Kooij, Woute W De Herde, Caspe H J Van Eijck, Oe L Kam, Martij Van Esse, Maarte O Van Ake, E. P. KrenningAbstract:Purpose Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled Somatostatin Analog [177Lu-DOTA0,Tyr3]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients and Methods Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Results Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Compl...
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radiolabeled Somatostatin Analog 177lu dota0 tyr3 octreotate in patients with endocrine gastroenteropancreatic tumors
Journal of Clinical Oncology, 2005Co-Authors: Dik J Kwekkeboom, Richard A Feelders, Jaap J M Teunisse, Willem H Akke, Pete P M Kooij, Woute W De Herde, Caspe H J Van Eijck, Janpaul Esse, Oe L Kam, E. P. KrenningAbstract:Purpose There are few treatment options for patients with metastasized or inoperable endocrine gastroenteropancreatic (GEP) tumors. Chemotherapy can be effective, but the response is usually less than 1 year. Here, we present the results of treatment with a radiolabeled Somatostatin Analog, [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Patients and Methods One hundred thirty-one patients with Somatostatin receptor-positive tumors were treated with up to a cumulative dose of 600 to 800 mCi (22.2 to 29.6 GBq) of 177Lu-octreotate. Results One patient developed renal insufficiency, and another patient developed hepatorenal syndrome. Creatinine clearance did not change significantly in the other patients. WHO hematologic toxicity grade 3 or 4 occurred after less than 2% of the administrations. We observed complete remission in three patients (2%), partial remission in 32 patients (26%), minor response (tumor diameter decrease of 25% to 50%) in 24 patients (19%), stable disease (SD) in 44 patients (35%), and...
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a single dose comparison of the acute effects between the new Somatostatin Analog som230 and octreotide in acromegalic patients
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Joost Van Der Hoek, Wouter W De Herder, Richard A Feelders, Aartjan Van Der Lely, P Uitterlinden, Viktor Boerlin, Christian Bruns, Kwai W Poon, Ian Lewis, Gisbert WeckbeckerAbstract:Treatment with the Somatostatin receptor (sst) subtype 2 predominant Analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst5. We compared the acute effects of octreotide and SOM230, a new Somatostatin Analog with high affinity for sst1,2,3,5 on hormone release in acromegalic patients. In a single-dose, proof-of-concept study, 100 μg octreotide and 100 and 250 μg SOM230 were given sc to 12 patients with active acromegaly. Doses of 100 and 250 μg SOM230 dose-dependently suppressed GH levels from 2–8 h after administration (−38 ± 7.7 vs. −61 ± 6.7%, respectively; P < 0.01). A comparable suppression of GH levels by octreotide and 250 μg SOM230 was observed in eight patients (−65 ± 7 vs. −72 ± 7%, respectively). In three patients, the acute GH-lowering effect of 250 μg SOM230 was significantly superior to that of octreotide (−70 ± 2 vs. −17 ± 15%, respectively; P < 0.01). I...
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a single dose comparison of the acute effects between the new Somatostatin Analog som230 and octreotide in acromegalic patients
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Joost Van Der Hoek, Wouter W De Herder, Richard A Feelders, Aartjan Van Der Lely, P Uitterlinden, Viktor Boerlin, Christian Bruns, Kwai W Poon, Ian Lewis, Gisbert WeckbeckerAbstract:Treatment with the Somatostatin receptor (sst) subtype 2 predominant Analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst(5). We compared the acute effects of octreotide and SOM230, a new Somatostatin Analog with high affinity for sst(1,2,3,5) on hormone release in acromegalic patients. In a single-dose, proof-of-concept study, 100 microg octreotide and 100 and 250 microg SOM230 were given s.c. to 12 patients with active acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%, respectively; P < 0.01). A comparable suppression of GH levels by octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7 vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering effect of 250 microg SOM230 was significantly superior to that of octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one patient, the GH-lowering effect of octreotide was better than that of SOM230. Tolerability for SOM230 was good. Glucose levels were initially slightly elevated after octreotide and SOM230, compared with control day, whereas insulin levels were only significantly suppressed by octreotide. We conclude that SOM230 is an effective GH-lowering drug in acromegalic patients with the potential to increase the number of patients controlled during long-term medical treatment.
Michael Koutsilieris - One of the best experts on this subject based on the ideXlab platform.
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randomized controlled clinical trial of a combination of Somatostatin Analog and dexamethasone plus zoledronate vs zoledronate in patients with androgen ablation refractory prostate cancer
Anticancer Research, 2006Co-Authors: Constantine S Mitsiades, John Bogdanos, Theodoros Dimopoulos, Dimitrios Karamanolakis, Constantine Milathianakis, Michael KoutsilierisAbstract:Background: As previously shown, the combination of standard androgen ablation therapy with Somatostatin Analog and dexamethasone in metastatic androgen ablation-refractory (stage D3) prostate cancer (PrCa) patients has a favorable profile of side-effects, durable objective antitumor activity (up to 60% partial response rate) and palliative effects. Bisphosphonates interfere with bone remodeling at the sites of PrCa bone metastases and have been postulated to have indirect and/or direct anti-PrCa activity. Materials and Methods: A randomized controlled clinical trial was conducted to compare a combination of Somatostatin Analog (octreotide 20 mg i.m. every 28 days) and oral dexamethasone (4 mg daily for 1 month, gradually reduced to 1 mg daily by the fourth month, with a 1 mg daily maintenance dose thereafter) plus zoledronate (4 mg i.v. every 4 weeks) vs. zoledronate only. All patients in both arms remained in basic androgen blockade throughout the study. Results: Thirty- eight stage D3 patients (mean age 72.8±6.8 years) were randomized to either treatment arm of the study. The trial was stopped after a pre-specified interim analysis met the criteria for early closure, i.e. significant difference in outcomes between the two treatment arms. Partial responses (PR, ≥50% PSA decline) were observed in 13 out of 20 patients with combination therapy vs. none with zoledronate. The combination therapy arm had significantly better outcome with respect to median progression- free survival (7.0 vs. 1.0 months, p 14 vs. 4 months
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combination of Somatostatin Analog dexamethasone and standard androgen ablation therapy in stage d3 prostate cancer patients with bone metastases
Clinical Cancer Research, 2004Co-Authors: Michael Koutsilieris, Constantine S Mitsiades, John Bogdanos, Theodoros Dimopoulos, Dimitrios Karamanolakis, Constantine Milathianakis, Athanassios TsintavisAbstract:Purpose: Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted “gold standard” treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of Somatostatin Analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone Analog or orchiectomy). Experimental Design: Thirty eight patients with stage D3 prostate cancer (mean age 71.8 ± 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and Somatostatin Analog (20 mg octreotide i.m. injections every 28 days). Results: Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, ≥50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7–17 months), median progression-free survival was 7 months (95% CI, 4.5–9.5 months), median overall survival was 14 months (95% CI, 10.7–17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9–20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9–19 months), without major treatment-related side effects. We observed a statistically significant ( P Conclusion: The combination therapy of dexamethasone plus Somatostatin Analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients.
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combination of lhrh Analog with Somatostatin Analog and dexamethasone versus chemotherapy in hormone refractory prostate cancer a randomized phase ii study
Urology, 2004Co-Authors: Meletios A Dimopoulos, Christos Kiamouris, Dimitra Gika, Charalambos Deliveliotis, Aris Giannopoulos, Anastasios Zervas, Christos Alamanis, Constantinos Constantinidis, Michael KoutsilierisAbstract:Abstract Objectives To evaluate prospectively the combination of a luteinizing hormone-releasing hormone Analog with a Somatostatin Analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone Analog with a Somatostatin Analog and dexamethasone has produced objective clinical responses in HRPC. Methods Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a Somatostatin Analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone Analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups. Results The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant). Conclusions The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone Analog, Somatostatin Analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.
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a combination therapy of dexamethasone and Somatostatin Analog reintroduces objective clinical responses to lhrh Analog in androgen ablation refractory prostate cancer patients
The Journal of Clinical Endocrinology and Metabolism, 2001Co-Authors: Michael Koutsilieris, Constantine S Mitsiades, Theodore Dimopoulos, Apostolos Ioannidis, Athanassios Ntounis, Theocharis LambouAbstract:We evaluated whether the combination of triptorelin, a LHRH Analog (LHRH-A), with dexamethasone and lanreotide, a Somatostatin Analog, can produce objective clinical responses in metastatic androgen ablation-refractory prostate cancer (stage D3) patients who have relapsed, after combined androgen blockade (LHRH-A plus antiandrogen) and antiandrogen withdrawal. Eleven stage D3 patients with diffuse bony metastases, who had progressed despite initial responses (lasting <12 months) to combined androgen blockade therapy and subsequently failed antiandrogen withdrawal, received oral dexamethasone (4 mg daily for the first month, tapered down to 2 mg after the first month and 1 mg after the second month, and continued on 1 mg thereafter) and lanreotide (30 mg im every 14 d) in combination with triptorelin (3.75 mg im every 28 d). Serum prostate-specific antigen, alkaline phosphatase, performance status, and bone pain were assessed monthly during therapy. Fasting blood glucose was measured biweekly, and serum IG...