Safety and Efficacy of the S-1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors

2017 ◽  
Vol 106 (4) ◽  
pp. 318-323 ◽  
Author(s):  
Jiuda Zhao ◽  
Hong Zhao ◽  
Yihebali Chi
Keyword(s):  
Neuroendocrine Tumors ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Response To Treatment ◽  
Endocrine Tumors ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Highly Active ◽  
Pancreatic Endocrine Tumors

Purpose: Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1/temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. Methods: A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75.00%) had failed 1 or more lines of treatment with somatostatin analogues, sunitinib, everolimus, anlotinib, or other chemotherapy regimens. The patients received S-1 at 40 mg/m2 orally twice daily on days 1-14 and temozolomide 200 mg orally once daily on days 10-14 of a 21-day cycle. The patients were followed up for evidence of object response, toxicity, and progression-free survival. Results: Response to treatment was assessed using RECIST 1.1. Eight patients (40.00%) achieved a partial response (PR), and another 8 (40.00%) had stable disease (SD). The clinical benefit rate (PR and SD) was 80.00%. The median progression-free survival was not achieved. Only 1 patient (5.00%) had grade 3 adverse events. Among the patients with NETs of different origins, 4 (40.00%) and 5 (50.00%) with pancreatic NETs attained PR and SD, respectively. Four (40.00%) and 3 patients (30.00%) with nonpancreatic NETs attained PR and SD, respectively. Conclusions: The STEM regimen is exceptionally highly active and well tolerated in patients with locally advanced or metastatic NETs. Even in patients who showed disease progression with previous therapies, it is still highly active. In this 20-patient study, the regimen appeared to be similarly active in pancreatic endocrine tumors and nonpancreatic NETs.

scholarly journals SAT-LB24 Association of Expression of Somatostatin Receptor 2 Subtype in Non-Pituitary Neuroendocrine Tumors With Response to Treatment With Somatostatin Analogues

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Abdullah Siddiqui ◽  
Alireza Hosseini ◽  
Roghayeh Marandi ◽  
Behrouz Salehian ◽  
Sue Chang
Keyword(s):  
Neuroendocrine Tumors ◽  
Patient Population ◽  
Expression Patterns ◽  
Somatostatin Receptor ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Response To Treatment ◽  
Proliferation Index ◽  
Free Survival ◽  
Additional Therapy

Abstract Background: The WHO classification of non-pituitary neuroendocrine tumors (NETs) includes grading (Ki67 proliferation index and mitosis index) and staging, and has been shown to be associated with outcome in this patient population. Neuroendocrine tumors show different somatostatin receptor (SSTR) subtypes expression, but their role has not been considered in tumor progression and prognosis. We hypothesize patients with non-pituitary NET, whose tumor tissues have higher specific SSTR2 expression patterns will experience better outcomes when treated with Somatostatin Analogues (SSA) compared to those with lower or absent SSTR2 expression. Methods and patients: City of Hope patients with non-pituitary NET who received SSA (Octreotide and Lanreotide) for over 1 year as treatment. The progression free survival was based on imaging studies (MRI, CAT scan of index tumor) on RECIST criteria, and expression of SSTR2 on the tumor obtained by surgery at the time of diagnosis. Immunohistochemical staining with a monoclonal antibody to SSTR2 performed at core pathology lab at City of Hope. H-scoring (intensity of immunostaining and percent of SSTR2 expression) was performed by one pathologist, and divided into four categories of 0-4. Pearson Chi-square test was used to assess the correlation between the SSTR2 score and 1-year progression. Outcome Measures: The effect of SSA therapy on 1 year progression-free survival (PFS), among patients with high intensity and percent of SSTR2 expression on the resected tumor tissue was compared to those with low or absent SSTR2 expression. Patient population: Of the 297 patients identified with non-pituitary neuroendocrine tumor, 70 patients satisfied the inclusion criteria and a total of 52 patients had data that was completely available for analysis. Results: Mean age of study subjects was 61+1.8 years. 26 were female and 26 were male. The primary sites for NET were: pancreas 17, jejunum 16, ileum 9; paraganglioma and pheochromocytomas 3, lung and thymus 3, gastric 2, and medullary thyroid carcinoma 1. The one-year progression was not significantly different among those with low and absent SSTR2 compared to high expression of SSTR2. Step wise analysis based on the scoring of the SSRT2 did not show significant 1 year progression. Age was not associated with PFS. However, the need for additional therapy (liver embolization, surgical resection) was signigicantly reduced amongst patients with presence of SSTR2. Conclusion: In this preliminary study there was no significant association between SSTR2 expression and Progression free survival, however the need for additional therapy in patients on somatostatin analogues were reduced among subjects with presence of SSTR2 expression

scholarly journals Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study

2019 ◽  
Vol 37 (28) ◽  
pp. 2571-2580 ◽  
Author(s):  
Alberto Carmona-Bayonas ◽  
Paula Jiménez-Fonseca ◽  
Ángela Lamarca ◽  
Jorge Barriuso ◽  
Ángel Castaño ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Failure Time ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Accelerated Failure Time Model ◽  
Endocrine Tumors ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Well Differentiated

PURPOSE Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

Safety and efficacy of docetaxel combined with cisplatin as induction chemotherapy followed by cisplatin concurrent chemoradiotherapy plus gemcitabine as adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A prospective and multicenter phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6064-6064
Author(s):  
Zhi Hui Wang ◽  
Peijian Peng ◽  
Siyang Wang ◽  
Yumeng Liu ◽  
Zhong Lin
Keyword(s):  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Induction Chemotherapy ◽  
Treatment Strategy ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy

6064 Background: Radiation therapy is the only curative treatment modality for nonmetastatic nasopharyngeal cancer (NPC). Concurrent chemoradiation (CCRT) is the standard treatment strategy for NPC in locally advanced stages. However, the results after such treatment are suboptimal. Clearly, novel treatment strategies are needed to further improve patients’ survival rates. This trial aimed to determine the safety and efficacy of a new treatment strategy. Methods: Patients with stage III – IVa-b NPC received TP (docetaxel 75 mg/m2, cisplatin 75 mg/m2 every 3 weeks for 2-3 cycles) followed by cisplatin chemotherapy concurrently with either 3-dimentional conformal radiation therapy or intensity-modulated radiation therapy plus gemcitabine (1000mg/m2 every 2 weeks for 2 cycles) as adjuvant chemotherapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.4.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-OIC-17011464. Results: From July 2010 to July 2017, 20 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 90% (3 complete responses [CRs] and 15 partial responses [PRs]) after two or three cycles of induction chemotherapy (ICT) and 100% (17 CRs and three PRs) after CCRT plus gemcitabine adjuvant chemotherapy, respectively. With a median follow-up time of 41 months, the 3-year overall survival rates were 90% (18/20,95% confidence interval [CI], 76.9%-100%).The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 80% (16/20,95% CI, 62.5%-97.5%), 85% (17/20,95% CI, 69.4%-100%),95% (19/20,95% CI, 85,4%-100%), respectively. The most frequent grade 3–4 toxicities were neutropenia (3/20,15%) and nausea (2/20,10%) after ICT and thrombocytopenia (6/20,30%) and leukopenia (6/20,30%) after CCRT plus gemcitabine adjuvant chemotherapy. Conclusions: Neoadjuvant TP followed by concurrent chemoradiation plus gemcitabine as adjuvant chemotherapy was well tolerated and produced promising outcomes in patients with LA-NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy. Clinical trial information: ChiCTR-OIC-17011464.

scholarly journals Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors

2007 ◽  
Vol 14 (2) ◽  
pp. 221-232 ◽  
Author(s):  
Eduardo Vilar ◽  
Ramón Salazar ◽  
Jose Pérez-García ◽  
Javier Cortes ◽  
Kjell Öberg ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Retrospective Studies ◽  
Response To Treatment ◽  
Biological Behavior ◽  
Endocrine Tumors ◽  
Ki 67 ◽  
Pancreatic Endocrine Tumors ◽  
Poorly Differentiated ◽  
Selection For

Neuroendocrine tumors (NETs) of the digestive tract are a heterogeneous group of rare malignancies. Three major subgroups can be defined: pancreatic endocrine tumors, carcinoid tumors, and poorly differentiated gastroenteropancreatic NETs. Classically, digestive NETS have been considered to have an indolent course characterized for prolonged stabilizations or slow progressions, but there are clear differences in terms of aggressiveness, clinical course, and response to treatment among them. Retrospective studies have identified several clinicopathological and immunohistochemical factors as angioinvasion and proliferative index assessed by Ki-67 expression, which predict biological behavior and correlate with survival. Chemotherapy regimens based on the combination of several active drugs such as streptozocin, doxorubicin, 5-fluorouracil, dacarbazine, and temozolomide show low response rates, which sets the need to improve the results of the medical treatment of these malignancies. This review will analyze the role of Ki-67 in digestive NETs under a clinical perspective and will suggest future fields for development of this approach that enable a better patient selection for chemotherapy. Also a comprehensive review of the literature about chemotherapy in NETs is presented.

PaFLO: Pazopanib with 5-fluorouracil, leucovorin, and oxaliplatin (FLO) as first-line treatment in advanced gastric cancer: A randomized phase II study of the  Arbeitsgemeinschaft internistische Onkologie (AIO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4138-TPS4138
Author(s):  
Kirstin Breithaupt ◽  
Dmitry Bichev ◽  
Mario Lorenz ◽  
Daniela Bohnen ◽  
Yasemin Dogan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Remission Rate ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Response To Treatment ◽  
Clinicopathological Parameters ◽  
Free Survival

TPS4138 Background: VEGF inhibition in gastric cancer shows promising improvement of remission rate and progression-free survival (Ohtsu et al., JCO 2011). Pazopanib is an orally available tyrosine kinase inhibitor (TKI) selectively inhibiting VEGFR-1, -2, -3, c-kit and PDGFR. It is approved for treating renal cell cancer. A phase-I trial showed good tolerability of pazopanib with full-dose FOLFOX in solid tumors (Brady et al., ASCO, 2009). FLO is a widely used combination for advanced gastric cancer recommended in national guidelines. Methods: 75 Patients with HER-2-negative locally advanced or metastatic adenocarcinoma of the stomach or the gastro-esophageal junction will be randomized in a 2:1 ratio to A: FLO (F 2600mg/m2 as 24h infusion, L 200mg/m2, O 85 mg/m2) d1 + pazopanib (800mg) d1-14 and B: FLO; repeated for 12 2-week cycles, followed by a maintenance therapy with pazopanib alone in A and an observation period in B until disease progression. Primary endpoint is progression-free survival rate (PFSR) at 6 months, secondary endpoints are PFSR at 9 and 12 months, median PFS, response rate, duration of response, toxicity, tolerability and overall survival. Additionally, we evaluate the predictive and prognostic relevance of PIGF, VEGF, and the respective soluble receptors sVEGFR1 and sVEGFR2 as biomarkers for clinicopathological parameters, clinical response to treatment and tumor volume change. Based on a phase-III trial demonstrating a 6-month PFSR of 44% with FLO (Al-Batran et al., 2008), we estimate a 6-month PFSR of 55% in the experimental group. Given an alpha error of 0.1 and a beta error of 0.2 in a Simon 2-stage minimax design, in the first stage ≥12 of 30 patients need to be progression free at 6 months to continue and after the second stage ≥25 of 50 patients should be progression free at 6 months to justify further evaluation. Randomization is performed to estimate selection bias according to pazopanib-specific exclusion criteria for comparison with historical data. Study protocol received ethics committee approval in November 2011 and is currently recruiting patients in 15 AIO centers.

Effectiveness and safety of nab-paclitaxel/gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma

2019 ◽  
Vol 26 (3) ◽  
pp. 603-611 ◽  
Author(s):  
María-José Nebot-Villacampa ◽  
Ricardo Zafra-Morales ◽  
Ascensión Alfaro-Olea ◽  
Raquel Marín-Gorricho ◽  
Andrea Casajús-Navasal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Safety Profile ◽  
Prognostic Markers ◽  
Single Case ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Free Survival ◽  
Metastatic Pancreatic Adenocarcinoma

Background Treatment based on nab-paclitaxel plus gemcitabine is one of the standard treatments for locally advanced or metastatic pancreatic adenocarcinoma. Not much information is available about its use in clinical practice. Looking for prognostic markers may aid in improving treatment plans for patients. Objective To describe the effectiveness and safety profile of nab-paclitaxel/gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma. We also tried to evaluate prognostic markers of response to treatment. Setting Retrospective descriptive study carried out in a tertiary hospital of Spain. Method Patients with locally advanced or metastatic pancreatic adenocarcinoma treated with nab-paclitaxel/gemcitabina between January 2014 and December 2017 were included in the analyses. Main outcome measure Effectiveness was measured in terms of overall survival, progression-free survival and response rate. To evaluate the safety profile, every adverse event from the start of the treatment and up to 10 days after its completion was registered. Results Fifty patients were included. Thirty-three (66%) had metastatic disease. Median overall survival was 8.8 months (95%CI: 5.1–12.5) and the median progression-free survival was 5.6 months (95%CI: 4.3–6.9). Relevance of carbohydrate antigen 19-9 baseline levels as prognostic response marker was confirmed, while neutrophil-to-lymphocyte ratio did not show conclusive results for overall survival. Safety profile was similar to that observed in clinical trials, with a single case of treatment discontinuation due to grade 3 neuropathy. Conclusion The studied schedule for locally advanced or metastatic pancreatic adenocarcinoma seems to be an effective therapeutic option, with an easy to manage toxicity profile, similar to other schedules used in pancreatic adenocarcinoma.

scholarly journals Low Expression of ARHI Is Associated with Shorter Progression-Free Survival in Pancreatic Endocrine Tumors

Neoplasia ◽  
2007 ◽  
Vol 9 (3) ◽  
pp. 181-IN2 ◽  
Author(s):  
Irene Dalai ◽  
Edoardo Missiaglia ◽  
Stefano Barbi ◽  
Giovanni Butturini ◽  
Claudio Doglioni ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Endocrine Tumors ◽  
Free Survival ◽  
Pancreatic Endocrine Tumors ◽  
Low Expression
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