scholarly journals Somatostatin Analogue Therapy in MEN1-Related Pancreatic Neuroendocrine Tumors from Evidence to Clinical Practice: A Systematic Review

2021 ◽  
Vol 14 (10) ◽  
pp. 1039
Author(s):  
Anna La Salvia ◽  
Franz Sesti ◽  
Chiara Grinzato ◽  
Rossella Mazzilli ◽  
Maria Grazia Tarsitano ◽  
...  

Introduction: Neuroendocrine neoplasms (NENs) are relatively rare and complex tumors that can be sporadic or hereditary, as in the context of multiple endocrine neoplasia type 1 (MEN1) where patients display a 70% lifelong risk of developing a pancreatic NENs (pNENs). To date, specific personalized treatment for pNENs in patients with MEN1 are lacking. The aim of this study was to systematically analyze the efficacy and safety of somatostatin analogue (SSA) treatment in patients affected by MEN1-related pNENs. Materials and Methods: We performed a systematic review of the literature, searching for peer-reviewed articles on SSA (octreotide or lanreotide) treatment in MEN1 associated with pNENs. Results: We selected 20 studies with a pooled population of 105 MEN1 patients with pNENs. Females were 58.5%, median age was 44 years (18–73). TNM stage at diagnosis was stage I-II in 84.8% and stage IV in 15.2%. The overall response rate (SD+PR+CR) was achieved in 88.3% of cases, with stable disease in 75.6% and objective response in 12.7% of patients. The safety profile was favorable with both SSA agents. Conclusions: SSAs appear to be an effective and safe treatment option for MEN1-related pNEN, either at localized or advanced stages.

1996 ◽  
Vol 14 (7) ◽  
pp. 1993-1999 ◽  
Author(s):  
C Wasserheit ◽  
A Frazein ◽  
R Oratz ◽  
J Sorich ◽  
A Downey ◽  
...  

PURPOSE A phase II study of paclitaxel and cisplatin in patients with advanced breast cancer was performed to determine the objective response rate and make further observations about the toxicity of this regimen. PATIENTS AND METHODS Patients were required to have histologically proven adenocarcinoma of the breast with no more than one chemotherapeutic treatment for advanced disease. Treatment consisted of paclitaxel 200 mg/m2 administered as a 24-hour intravenous (i.v.) infusion followed by cisplatin 75 mg/m2 i.v. Patients received granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously on day 3 until WBC recovery. Cycles were repeated every 21 days. Patients continued to receive therapy until disease progression or unacceptable toxicity. RESULTS Forty-four patients entered the trial. Forty-two patients were assessable for response. Nineteen patients (43%) had no prior chemotherapy and 41 had no chemotherapy for metastatic disease. The median number of cycles administered per patient was five (range, one to seven). There were five complete responses (CRs) (11.9%) and 17 partial responses (PRs) (40.5%), with an overall response rate of 52.4% (95% confidence interval [CI], 36.4% to 68.0%). Nine patients had stage III disease. The response rate for this group was 66.7% (95% CI, 33.0% to 92.5%), with three CRs and three PRs. Among 35 patients with stage IV disease, there were two CRs and 14 PRs, with an overall response rate of 48.5% (95% CI, 30.8% to 66.5%). Overall, the median response duration was 10.6 months. Thirty patients (68%) developed transient grade 4 neutropenia. Cumulative neuropathy was the major dose-limiting toxicity. After five cycles of chemotherapy, 96% of patients had at least grade 1 neurotoxicity and 52% had at least grade 2 neurotoxicity. One patient had a toxic death after cycle 1 of therapy. CONCLUSION The combination of paclitaxel and cisplatin as first-line chemotherapy for women with advanced breast cancer is an active regimen. However, the cumulative neurotoxicity was significant and dose-limiting in the majority of patients.


Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013296
Author(s):  
Jisun Hwang ◽  
Hee Mang Yoon ◽  
Beom Hee Lee ◽  
Pyeong Hwa Kim ◽  
Kyung Won Kim

Background and Objectives:Although the recent approval of selumetinib is expected to transform the management of children with Neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable PN, no systematic review has summarized their efficacy and safety based on the latest studies. This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1Methods:Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. The pooled objective response rates (ORRs) and disease control rates (DCRs) were calculated using the DerSimonian–Laird method based on random-effects modeling. The pooled proportion of adverse events (AEs) was also calculated. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system.Results:Five studies involving 126 patients were included in our analysis. The studies had a very low to moderate quality of the evidence. The pooled ORR was 73.8% (95% CI: 57.3–85.5%), and the DCR was 92.5% (95% CI: 66.5–98.7%). The two most common AEs were diarrhea, which had a pooled rate of 63.8% (95% CI, 52.9–73.4%) and an increase in creatine kinase levels, which had a pooled rate of 63.3% (95% CI, 35.6–84.3%).Discussion:Our results indicate that selumetinib is an effective and safe treatment for pediatric patients with symptomatic, inoperable plexiform neurofibromas. Further larger-scale randomized controlled studies are needed to confirm the long-term outcome of patients treated with this drug.


2019 ◽  
Vol 25 (35) ◽  
pp. 5376-5387 ◽  
Author(s):  
Apostolos V Tsolakis ◽  
Athanasia Ragkousi ◽  
Miroslav Vujasinovic ◽  
Gregory Kaltsas ◽  
Kosmas Daskalakis

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3037-3037
Author(s):  
Eo Jin Kim ◽  
Dae-Hyun Ko ◽  
Wonjun Ji ◽  
Jin Kyung Rho ◽  
Jae Cheol Lee ◽  
...  

3037 Background: Despite the increased promise of checkpoint inhibitors in the treatment of lung cancer, the overall response rate is approximately 30% with up to 30% moderate to severe side effects. Natural killer (NK) cells have recently been implicated in antitumor response to immune checkpoint inhibitors. SNK01 is a novel non-genetically modified autologous natural killer cell therapy with enhanced cytotoxicity which has been found to have tumoricidal effects against several lung cancer cell lines. Methods: 18 patients with Stage IV NSCLC (PD-L1+, EGFR-, ALK-) who all failed prior frontline platinum-based therapy were randomized 2:1 to Pembrolizumab every three weeks +/- 6 weekly infusions of SNK01 at either 2 x 109 or 4 x 109 cells per infusion. Primary endpoint is safety and secondary endpoints are objective response rate (ORR), progression-free survival (PFS), overall survival (OS), time to progression (TPP), and quality of life (QoL). Results: 14 patients have been enrolled up to date and 9 have completed treatment. Median age is 69 (52-73). Two patients discontinued treatment prior to receiving their first dose of SNK01 due to Grade 3 toxicity to Pembrolizumab. Three patients have completed therapy with Pembrolizumab alone and all had progressive disease. Three patients have completed Pembrolizumab with 2 x 109 SNK01 and three patients have completed Pembrolizumab with 4 x 109 SNK01. Of patients receiving full combination therapy, there have been no adverse events or any reported toxicity while overall QoL has been improved. The week 9 overall response rate in the combination group is 66% using iRECIST (3/6 cPR, 1/6 PR). All remaining planned patients are currently being enrolled and a full update will be presented. Conclusions: These preliminary results demonstrate that combination therapy with Pembrolizumab and SNK01 is very safe and even appears to reduce checkpoint associated toxicity while increasing overall tumor response compared to Pembrolizumab monotherapy alone in Stage IV NSCLC patients who have failed prior platinum-based treatment.


2019 ◽  
Author(s):  
Rahul Kanabar ◽  
Jorge Barriuso ◽  
Mairead McNamara ◽  
Was Mansoor ◽  
Richard Hubner ◽  
...  

2020 ◽  
Author(s):  
Anthony Pease ◽  
Clement Lo ◽  
Arul Earnest ◽  
Velislava Kiriakova ◽  
Danny Liew ◽  
...  

<b>Background: </b>Time-in-range is a key glycaemic metric, and comparisons of management technologies for this outcome are critical to guide device selection. <p><b> </b></p> <p><b>Purpose: </b>We conducted a systematic review and network meta-analysis to compare and rank technologies for time in glycaemic ranges.</p> <p> </p> <p><b>Data sources: </b>We searched All Evidenced Based Medicine Reviews, CINAHL, EMBASE, MEDLINE, MEDLINE In-Process and other non-indexed citations, PROSPERO, PsycINFO, PubMed, and Web of Science until 24 April, 2019.</p> <p> </p> <p><b>Study selection: </b>We included randomised controlled trials <u>></u>2 weeks duration comparing technologies for management of type 1 diabetes in adults (<u>></u>18 years of age), excluding pregnant women. </p> <p> </p> <p><b>Data extraction: </b>Data were extracted using a predefined template. Outcomes were percent time with sensor glucose levels 3.9–10.0mmol/l (70–180mg/dL), >10.0mmol/L (180mg/dL), and <3.9mmol/L (70mg/dL). </p> <p><b> </b></p> <p><b>Data synthesis: </b>We identified 16,772 publications, of which 14 eligible studies compared eight technologies comprising 1,043 participants. Closed loop systems lead to greater percent time-in-range than any other management strategy and was 17.85 (95% predictive interval [PrI] 7.56–28.14) higher than usual care of multiple daily injections with capillary glucose testing. Closed loop systems ranked best for percent time-in-range or above range utilising surface under the cumulative ranking curve (SUCRA–98.5 and 93.5 respectively). Closed loop systems also ranked highly for time below range (SUCRA–62.2). </p> <p><b> </b></p> <p><b>Limitations: </b>Overall risk of bias ratings were moderate for all outcomes. Certainty of evidence was very low.</p> <p><b> </b></p> <p><b>Conclusions: </b>In the first integrated comparison of multiple management strategies considering time-in-range, we found that the efficacy of closed loop systems appeared better than all other approaches. </p>


2018 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Mingxia Wang ◽  
Guanqi Wang ◽  
Haiyan Ma ◽  
Baoen Shan

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.


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