scholarly journals Advances and Current Concepts in the Medical Management of Gastroenteropancreatic Neuroendocrine Neoplasms

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Krystallenia I. Alexandraki ◽  
Aggeliki Karapanagioti ◽  
Ioannis Karoumpalis ◽  
Georgios Boutzios ◽  
Gregory A. Kaltsas
Keyword(s):  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Potential Effect ◽  
Tumor Burden ◽  
Molecular Signature ◽  
Phase Iii ◽  
Neuroendocrine Neoplasms ◽  
Gastroenteropancreatic Neuroendocrine Neoplasms ◽  
Develop Disease Progression ◽  
Phase Iii Trials

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare and heterogeneous group of tumors presenting as localised or metastatic disease and in a subset with distinct clinical syndromes. Treatment is aimed at controlling the functional syndrome, eradicating the tumor, and/or preventing further tumor growth. Surgery is the treatment of choice in removing the primary tumor and/or reducing tumor burden but cannot be applied to all patients. Somatostatin analogs (SS-analogs) obtain control of functional syndromes in the majority of GEP-neuroendocrine tumors (NETs); phase III trials have shown that SS-analogs can be used as first-line antiproliferative treatment in patients with slow-growing GEP-NETs. The role of the recently approved serotonin inhibitor, telotristat ethyl, and gastrin receptor antagonist, netazepide, is evolving. Streptozotocin-based chemotherapy has been used for inoperable or progressing pancreatic NENs but the orally administered combination of capecitabine/temozolomide is becoming more popular due to its better tolerability and potential effect in other GEP-NENs. Phase III trials have shown efficacy of molecular targeted therapies in GEP-NETs and of radionuclide treatment in patients with midgut carcinoid tumors expressing somatostatin receptors. Most patients will develop disease progression necessitating further therapeutic options. A combination of currently available treatments along with the molecular signature of each tumor will guide future treatment.

CVP alternating with fludarabine (CVP/F) chemotherapy prior to idiotype vaccination for follicular lymphoma (FL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8065-8065
Author(s):  
W. Z. Ai ◽  
F. J. Hsu ◽  
J. M. Timmerman ◽  
D. Czerwinski ◽  
B. Taidi ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Tumor Burden ◽  
Phase Iii ◽  
The Novel ◽  
Effective Immune Response ◽  
Best Response ◽  
Time To Treatment Failure ◽  
Phase Iii Trials ◽  
Idiotype Vaccine

8065 Background: Reducing the tumor burden prior to vaccination facilitates an effective immune response (IR) against the idiotype in FL. In this context, we evaluated the efficacy and toxicity of a novel cytoreductive regimen, CVP/F. Methods: Newly diagnosed, advanced stage FL patients (pt) were treated with CVP (cyclophosphamide 400 mg/m2 PO d1–5, vincristine 2 mg d 1, prednisone 100 mg/m2 d1–5) alternating with F (25 mg/m2 IV d1–5) every 21 days for 2 cycles beyond best response (maximum 8). Pt judged to be cytoreduced adequately were vaccinated monthly × 5 with idiotype protein made from their FL. Results: Among 34 enrolled pt, median age was 45 years (yr), and FLIPI scores were: 18% low, 71% intermediate and 12% high. 38% pt had grade 1 and 62% had grade 2 FL. There were no toxic deaths or opportunistic infections. With 233 cycles (117 CVP and 116 F) given to 33 evaluable pt, neutropenic fever occurred in 7 cycles (3%). 20 cycles (17%) of CVP and 29 cycles (25%) of F were dose reduced for leukopenia. 18 pt (53%) achieved a CR (16) or CRu (2), and 13 pt (38%) had a PR. 22 pt (65%) treated with CVP/F proceeded to vaccination; 10 additional pt (29%) were vaccinated after secondary chemotherapy was given for further cytoreduction. At median follow-up of 11.2 yr, 15-yr overall survival (OS) was 85%. Two of 5 deaths occurred without lymphoma progression. TTF (time to treatment failure = second treatment, relapse, death) at 11 yr was 38%. Anti-idiotype antibody and T cell IR were seen in 44% and 31% pt, respectively. There were no differences in TTF or OS according to IR. Conclusions: CVP/ F was effective in advanced FL, comparing favorably with our historical experience with CVP in terms of CR rate, proportion proceeding to vaccination, TTF and OS after vaccination. This favorable outcome may have been due to the novel alternating CVP/F cytoreductive regimen, idiotype vaccination or both. The idiotype vaccine is now being tested in phase III trials. The CVP/F regimen also warrants further evaluation. No significant financial relationships to disclose.

Clinical importance of including new and nontarget lesion assessment of disease progression (PD) to predict overall survival (OS): Implications for randomized phase II study design.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2543-2543 ◽  
Author(s):  
William Leonard Mietlowski ◽  
Weichao Bao ◽  
Patricia Ann Wood ◽  
Denise E Williams ◽  
Mona El-Hashimy ◽  
...  
Keyword(s):  
Decision Making ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Target Lesion ◽  
Tumor Burden ◽  
Percentage Change ◽  
Phase Iii ◽  
Risk Of Death ◽  
Randomized Phase Ii ◽  
Phase Iii Trials

2543 Background: Fridlyand (2011) retrospectively compared PFS vs. change in tumor burden as a primary endpoint in phase II non-small cell lung cancer (NSCLC) trials to inform phase III decision making and found the use of PFS was superior. Since the classic tumor burden model only uses measurements of target lesions, we investigated whether the model could be strengthened by incorporating new and non-target lesion progression. The ability to use a strong tumor burden model has the benefit of potentially earlier decision making and considerable timeline savings. Methods: We analyzed five phase III trials of combination chemotherapy ± targeted therapies with an OS primary endpoint: 1st, 2nd line NSCLC (ATTRACT-1, -2), 1st, 2nd line colorectal carcinoma (CONFIRM-1, -2), and 2nd line ovarian cancer (EPO906A2303). We applied Cox’s proportional hazards model to OS using the covariates of baseline tumor burden, 1st tumor assessment percentage change from baseline, new lesions, and non-target PD. Results: See table. Conclusions: We show that predictive models for OS should consider new and non-target lesions for PD, as well as target lesion tumor burden, findings independently corroborated by Suzuki (2011). We propose a longitudinal rank-based randomized phase II design, ranking a patient’s risk of death, differentially weighting PDs by type and time of PD, and percentage change in tumor burden. This may be more informative for phase II decision making for phase III trials based on OS, than PFS which only uses time of PD. Further studies with other tumor types and treatment modalities are warranted. [Table: see text]

scholarly journals Refractory carcinoid syndrome: a review of treatment options

2016 ◽  
Vol 9 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Rachel P. Riechelmann ◽  
Allan A. Pereira ◽  
Juliana F. M. Rego ◽  
Frederico P. Costa
Keyword(s):  
Carcinoid Syndrome ◽  
Treatment Options ◽  
Somatostatin Analogs ◽  
Current Treatment ◽  
Phase Iii ◽  
Treatment Sequence ◽  
First Line ◽  
Phase Iii Trials ◽  
Recent Phase ◽  
Well Differentiated

Carcinoid syndrome (CSy) is a constellation of symptoms that may commonly present in patients with well differentiated neuroendocrine tumors (NETs), with somatostatin analogs (SSAs) being the first-line option for symptom management. However, symptomatic progression eventually occurs and in this scenario of a refractory CSy; several treatment options have been studied such as dose escalation of SSA, interferon and liver-directed therapies. Nevertheless, recent phase III trials have contributed to the understanding and management of this condition. We performed a comprehensive review of interventional studies examining refractory CSy to provide the evidence for current treatment options and propose a treatment sequence.

scholarly journals Strategies Towards Improving Clinical Outcomes of Peptide Receptor Radionuclide Therapy

2021 ◽  
Vol 23 (4) ◽  
Author(s):  
N.S. Minczeles ◽  
J. Hofland ◽  
W.W. de Herder ◽  
T. Brabander
Keyword(s):  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Phase Iii ◽  
Neuroendocrine Neoplasms ◽  
Low Grade ◽  
Renal Protection ◽  
Peptide Receptor ◽  
Phase Iii Trials ◽  
Third Line

Abstract Purpose of Review Peptide receptor radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3] octreotate is an effective and safe second- or third-line treatment option for patients with low-grade advanced gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). In this review, we will focus on possible extensions of the current use of PRRT and on new approaches which could further improve its treatment efficacy and safety. Recent Findings Promising results were published regarding PRRT in other NENs, including lung NENs or high-grade NENs, and applying PRRT as neoadjuvant or salvage therapy. Furthermore, a diversity of strategic approaches, including dosimetry, somatostatin receptor antagonists, somatostatin receptor upregulation, radiosensitization, different radionuclides, albumin binding, alternative renal protection, and liver-directed therapy in combination with PRRT, have the potential to improve the outcome of PRRT. Also, novel biomarkers are presented that could predict response to PRRT. Summary Multiple preclinical and early clinical studies have shown encouraging potential to advance the clinical outcome of PRRT in NEN patients. However, at this moment, most of these strategies have not yet reached the clinical setting of randomized phase III trials.

scholarly journals Neuroendocrine tumor disease: an evolving landscape

2012 ◽  
Vol 19 (5) ◽  
pp. R163-R185 ◽  
Author(s):  
Andrea Frilling ◽  
Goran Åkerström ◽  
Massimo Falconi ◽  
Marianne Pavel ◽  
Jose Ramos ◽  
...  
Keyword(s):  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Delayed Diagnosis ◽  
Surgical Techniques ◽  
Positron Emission Tomography Imaging ◽  
Symptomatic Treatment ◽  
Neuroendocrine Neoplasms ◽  
Mesenteric Lymph Nodes ◽  
Ki 67 ◽  
Endoscopic Ablation

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEP-NENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even in advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used biomarker but has limitations as does the proliferative marker Ki-67%, which is often used for tumor grading and determination of therapy. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy but requires validation. Identification of NENs that express somatostatin receptors (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging using novel radiolabeled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure; however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity in small intestinal NENs. There is a place for streptozotocin, temozolomide, and capecitabine in the management of pancreatic NENs, while new agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have shown efficacy in these lesions.

scholarly journals Molecular Imaging using PET/CT Applying 68Ga-Labeled Tracers and Targeted Radionuclide Therapy: Theranostics on the Way to Personalized Medicine

2013 ◽  
Vol 47 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Richard P Baum ◽  
Harshad R Kulkarni
Keyword(s):  
Molecular Imaging ◽  
Personalized Medicine ◽  
Radionuclide Therapy ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Neuroendocrine Neoplasms ◽  
Targeted Radionuclide Therapy ◽  
Beta Emitters ◽  
Pet Ct ◽  
The Way

ABSTRACT Theranostics is an acronym, which exemplifies the togetherness of diagnostics and therapeutics in the individualized management of disease. The key to personalized medicine in cancer is to determine the molecular phenotypes of neoplasms, so that specific probes can be selected to target the tumor and its microenvironment. Molecular imaging and radionuclide therapy using a particular probe is based on this premise. Neuroendocrine neoplasms express somatostatin receptors, enabling the use of somatostatin analogs for molecular imaging, when labeled with the positron-emitter 68Ga for receptor positron emission tomography/computed tomography (PET/CT), and targeted radionuclide therapy, when labeled with beta-emitters 90Y and 177Lu. How to cite this article Kulkarni HR, Baum RP. Molecular Imaging using PET/CT Applying 68Ga-Labeled Tracers and Targeted Radionuclide Therapy: Theranostics on the Way to Personalized Medicine. J Postgrad Med Edu Res 2013; 47(1):47-53.

Relation between baseline LDH and tumor burden in advanced melanoma in two phase III trials of oblimersen-dacarbazine (OBL-DTIC) versus DTIC.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 8557-8557
Author(s):  
C. Lebbé ◽  
J. J. Grob ◽  
A. Y. Bedikian ◽  
C. Garbe ◽  
C. Robert ◽  
...  
Keyword(s):  
Tumor Burden ◽  
Advanced Melanoma ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Trials
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