scholarly journals Efficacy of somatostatin analogues in the treatment of neuroendocrine tumours based on the results of recent clinical trials

2014 ◽  
Vol 155 (48) ◽  
pp. 1908-1912 ◽  
Author(s):  
Péter Igaz
Keyword(s):  
Tumour Growth ◽  
Neuroendocrine Tumours ◽  
Hormone Secretion ◽  
Progression Free Survival ◽  
Symptomatic Treatment ◽  
Somatostatin Analogues ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Free Survival ◽  
Clinical Observations

Due to their inhibitory effects on hormone secretion, somatostatin analogues are of pivotal importance in the symptomatic treatment of hormone-secreting neuroendocrine tumours. Although several earlier clinical observations supported the view that these biological agents are capable of inhibiting the growth of neuroendocrine tumours, the PROMID study published in 2009 was the first to confirm the inhibitory effect of octreotide on tumour growth and demonstrated the prolongation of progression free survival. These findings have been confirmed and extended by the most recent CLARINET trial with lanreotide published in 2014. Somatostatin analogues are capable of inhibiting tumour growth and stabilizing disease irrespective of the hormonal activity of the tumour and, therefore, their applicability is expected to be extended to the treatment of hormonally inactive neuroendocrine tumours, as well. Orv. Hetil., 2014, 155(48), 1908–1912.

Alkylating agent rechallenge in metastatic pancreatic neuroendocrine tumours

2021 ◽  
Author(s):  
Ophelie De Rycke ◽  
Thomas Walter ◽  
Marine Perrier ◽  
Olivia Hentic ◽  
Catherine Lombard-Bohas ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Free Survival ◽  
Mgmt Expression ◽  
Pancreatic Neuroendocrine Tumours

A rechallenge is common after initial efficacy of alkylating-based chemotherapy (ALK) in pancreatic neuroendocrine tumors (PanNET). High MGMT expression seems associated with lower response to ALK. We aimed to evaluate the efficacy and toxicity of ALK rechallenge in PanNET. Secondly, to assess the evolution of MGMT expression under ALK. All consecutive patients with advanced PanNETs who received initial ALK (achieving tumor control) followed by a pause > 3 months, then an ALK rechallenge (ALK2) upon progression were retrospectively studied (Cohort A). Primary endpoint was progression-free survival under ALK2 (PFS2). The MGMT expression was retrospectively assessed by immunohistochemistry (H-score) in consecutive PanNET surgically resected following ALK (Cohort B). We foud that cohort A included 62 patients (median Ki67 8%), for which ALK1 followed by pause achieved an objective response rate of 55%, and a PFS1 of 23.7 months (95% IC, 19.8-27.6). ALK2 achieved no objective response, and stability in 62% of patients. The median PFS2 was 9.2 months (IC 95% 7.1-11.3). At multivariable analysis, a hormonal syndrome (p=0.032) and a pause longer than 12 months (p=0.041) were associated with a longer PFS2. In the cohort B (17 patients), the median MGMT H-score increased from 45 (IQR 18-105) before ALK, to 100 (IQR 56-180) after ALK (p=0.003). We conclude that after initial efficacy of ALK treatment, a pause followed by ALK rechallenge might be appropriate to prolong tumor control, improve quality of life and limit long-term adverse events. Increased MGMT expression under ALK might explain low efficacy of ALK rechallenge.

[177Lu]Lu-DOTA-TATE Versus Standard of Care in Adult Patients With Gastro-Enteropancreatic Neuroendocrine Tumours (GEP-NETS): A Cost-Consequence Analysis From an Italian Hospital Perspective

2021 ◽  
Author(s):  
Francesca Spada ◽  
Davide Campana ◽  
Giuseppe Lamberti ◽  
Riccardo Laudicella ◽  
Renato Dellamano ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Neuroendocrine Tumours ◽  
Treatment Options ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Somatostatin Analogues ◽  
Adult Patients ◽  
Hospital Perspective ◽  
Cost Consequence

Abstract Purpose To assess and compare clinical outcomes and costs, to the Italian healthcare system, of three therapeutic options approved in the management of adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs). Methods We compared the efficacy, safety and costs of [177Lu]Lu-DOTA-TATE, everolimus (both originator and generic products) and sunitinib in patients with advanced GEP-NETs (NET G1 and G2) that had progressed following treatment with somatostatin analogues (SSAs). A cost-consequence model was developed and validated by a panel of clinical experts from three NET reference centres in Italy. The clinical outcomes included in the model were median progression-free survival and the incidence of grade 3 or 4 adverse events (AEs), as reported in pivotal clinical trials. The costs for acquisition and administration of each treatment, and of managing AEs, were calculated from the perspective of the Italian national health service. Treatment costs per progression-free month were calculated separately for patients with NETs of pancreatic (PanNETs; all three treatments) and gastrointestinal (GI-NETs; [177Lu]Lu-DOTA-TATE and everolimus only) origin. Results In patients with PanNETs, total costs per progression-free month were €2989 for [177Lu]Lu-DOTA-TATE, €4975 for originator everolimus, €3472 for generic everolimus, and €5337 for sunitinib. In patients with GI-NETs, total costs per progression-free month were €3189 for [177Lu]Lu-DOTA-TATE, €4990 for originator everolimus, and €3483 for generic everolimus. Conclusions [177Lu]Lu-DOTA-TATE was associated with lower costs per progression-free month versus relevant treatment options in patients with GI-NETs or PanNETs (NET G1–G2; progressed following SSA treatment), although acquisition and administration costs are higher. These findings provide further economic arguments in the overall context of treatment decision making.

NCOG-33. GROWTH DYNAMICS OF INCIDENTAL MENINGIOMAS - A 10-YEAR PROSPECTIVE STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi159-vi159
Author(s):  
Torbjørn Austveg Strømsnes ◽  
Morten Lund-Johansen ◽  
Geir Olve Skeie ◽  
Bente Sandvei Skeie
Keyword(s):  
Growth Rate ◽  
Tumour Growth ◽  
Growth Dynamics ◽  
Progression Free Survival ◽  
Early Observation ◽  
Active Monitoring ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Observation Period

Abstract There is no consensus for the management of incidental meningiomas. To evaluate the natural history, we assessed tumour growth dynamics during 10 years of active monitoring of 62 patients (45 female and mean age 63.9) harbouring 68 tumours. Radiological and clinical data was obtained was obtained biannually for two years, then annually the following eight. Thirty-six patients (38 tumours) were referred to treatment and/or died of unrelated causes (n=5) within 5 years. The remaining were monitored for up to 10 years. Mean overall survival was at 128 months (95% CI: 118.8-136.7). Median progression free survival was 34 months (95% CI: 14.7-53.3). Median time for growth requiring intervention was 46 months (95% CI: 23.5-68.5). All tumours with self-limiting growth at 5 years (57.9 %) were still stable or reducing in size at 10 years. Mean growth rate decreased from 0.27 cm3/year (95% CI: 0.10-0.43) during the early observation period (0-5 years) to 0.09 cm3/year (95% CI: -0.02-0.21) in the late observation period. No tumours were referred to treatment during the late observation period. Two patients, both with verified WHO2 grade meningiomas succumbed to the disease, seven and eight years after diagnosis. No other patients developed symptoms and none other of the 18 total mortalities were meningioma related. Most clinical and radiological events occur within 5 years after diagnosis. Our findings suggests that if tumour growth slows down during the first 5 years of monitoring, this trend will continue. Clinical follow-up should be sufficient when a self-limiting growth pattern has been established.

scholarly journals Expression of SOAT1 in Adrenocortical Carcinoma and Response to Mitotane Monotherapy: An ENSAT Multicenter Study

2020 ◽  
Vol 105 (8) ◽  
pp. 2642-2653 ◽  
Author(s):  
Isabel Weigand ◽  
Barbara Altieri ◽  
Amanda M F Lacombe ◽  
Vittoria Basile ◽  
Stefan Kircher ◽  
...  
Keyword(s):  
Protein Expression ◽  
Treatment Response ◽  
Adrenocortical Carcinoma ◽  
Advanced Disease ◽  
Hormone Secretion ◽  
Single Agent ◽  
Objective Response ◽  
Drug Effects ◽  
Progression Free Survival ◽  
Free Survival

Abstract Context Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20%, and adverse drug effects are frequent. To date, there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1), which leads to endoplasmic reticulum stress and cell death in ACC cells. Objective To investigate SOAT1 protein expression as a marker of treatment response to mitotane. Patients A total of 231 ACC patients treated with single-agent mitotane as adjuvant (n = 158) or advanced disease therapy (n = 73) from 12 ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded specimens. Setting Retrospective study at 12 ACC referral centers. Main outcome measure Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Results Sixty-one of 135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumor stage, and Ki67 index, RFS (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 0.61-1.85; P = 0.82), and DSS (HR = 1.30; 95% CI, 0.58-2.93; P = 0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR = 1.34; 95% CI, 0.63-2.84; P = 0.45) and DSS (HR = 0.72; 95% CI, 0.31-1.70; P = 0.45) were comparable and response rates not significantly different. Conclusions SOAT1 expression was not correlated with clinical endpoints RFS, PFS, and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival.

scholarly journals Hyperprogressive disease during nivolumab or irinotecan treatment in patients with advanced gastric cancer

ESMO Open ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. e000488 ◽  
Author(s):  
Masahiko Aoki ◽  
Hirokazu Shoji ◽  
Kengo Nagashima ◽  
Hiroshi Imazeki ◽  
Takahiro Miyamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Survival Benefit ◽  
Poor Prognosis ◽  
Tumour Growth ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prior Therapy ◽  
Hyperprogressive Disease

BackgroundNivolumab showed a survival benefit for advanced gastric cancer (AGC). However, an acceleration of tumour growth during immunotherapy, (hyperprogressive disease, HPD) has been reported in various cancers. This study reviewed the HPD in patients with AGC treated with nivolumab or irinotecan.MethodsThe subjects of this retrospective study were patients with AGC with measurable lesions, and their tumour growth rates (TGR) during nivolumab or irinotecan were compared with those during prior therapy. HPD was defined as an increase in TGR more than twofold.Results34 and 66 patients received nivolumab and irinotecan in third or later line between June 2009 and September 2018 at our hospital; 22 patients receiving nivolumab had prior treatment with irinotecan, and one patient received irinotecan after nivolumab. Nivolumab and irinotecan showed no differences in disease control rates (38.2% and 34.8%) and in progression-free survival (PFS) (HR 1.1, 95% CI 0.7 to 1.6, p=0.802). The incidence of HPD was slightly higher after nivolumab (29.4%) than after irinotecan (13.5%) (p=0.0656), showing no differences in background between the patients with and without HPD. Compared between HPD and PD other than HPD after nivolumab, the HRs for PFS and overall survival (OS) were 1.1 (95% CI 0.5 to 2.7; p=0.756), and 2.1 (95% CI 0.7 to 5.8; p=0.168), but such clear difference in OS was not observed after irinotecan.ConclusionsHPD was observed more frequently after nivolumab compared with irinotecan, which was associated with a poor prognosis after nivolumab but not so clearly after irinotecan.

High-Dose Imatinib Mesylate Treatment in Patients (Pts) with Previously Untreated Early Chronic Phase (CP) Chronic Myeloid Leukemia (CML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 999-999 ◽  
Author(s):  
Jorge Cortes ◽  
Moshe Talpaz ◽  
Susan O’Brien ◽  
Francis Giles ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Standard Dose ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
P Value ◽  
High Dose ◽  
Free Survival ◽  
Clinical Observations ◽  
Pre Treatment ◽  
Grade 3

Abstract Imatinib has become the treatment of choice for most with CML. The standard dose (SD) for CP CML is 400 mg daily, but pre-clinical and clinical observations suggest that higher doses (HD) may be more effective. We have treated 222 with previously untreated CML in early CP with imatinib in 3 consecutive trials: one using SD imatinib (400 mg/day) (n=50; all entered in April 2001) and 2 subsequent trials using 400 mg twice daily (total dose 800 mg/day) (n= 172; from June 2001 until present). The 2 HD trials had identical inclusion criteria and will be considered together for this analysis. Pts followed for at least 3 months (mo) are evaluable (n=210) for this report (n=49 at 400mg, 161 at 800 mg). The median age was 48 years (range, 15 to 84); platelets were >450 x109/L in 71 pts (34%), 78 (37%) had peripheral blood (PB) blasts, and 11 (5%) had clonal evolution. Sokal risk group classification was good in 128 (61%) pts, intermediate in 61 (29%) pts, and poor in 21 (10%) pts. There was no difference in pre-treatment characteristics between the standard SD and HD groups. The results at 18 months are as follows: Response % Response p value* 400 mg/day 800 mg/day CR=Complete remission, Molecular Major=BCR-ABL/ABL <0.05%, Molecular CR=BCR-ABL undetectable (confirmed by nested PCR), *p value by log-rank Median follow-up (months) 36 19 Cytogenetic CR 81 96 0.0002 Cytogenetic Major 99 93 0.15 Molecular Major 47 67 0.0007 Molecular CR 8 24 0.02 Four pts treated with SD have transformed (3 to BP, 1 to AP) and 3 (2 to BP, 1 to AP) in the HD groups (p=0.05) (median time to transformation 11 mo, range 3 to 27). Estimated progression-free survival at 12 mo is 92% in the SD group and 99% in the HD group (p=0.42) (p=0.12 for the estimated transformation-free-survival, 94% and 99% for SD and HD at 12 mo). 4 have died (1 in SD and 3 in HD). Extramedullary toxicity was similar in the 2 groups, but myelosuppression was more common with HD, with grade ≥3 anemia, neutropenia and thrombocytopenia occurring in 7%, 39%, and 27% of pts receiving HD, respectively, and 4%, 20% and 12% of pts receiving SD. At 12 mo, the median actual dose for the HD group is still 800mg, with 40/112 (36%) evaluable having required dose reduction. This compares with 7/43 (14%) of those treated with SD. We conclude that high-dose imatinib results in higher rates of complete cytogenetic and molecular remissions, with some increase in myelosuppression.

Bronchial neuroendocrine tumors: A retrospective review of management and outcomes in 116 patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17543-e17543
Author(s):  
Marinos Pericleous ◽  
Heather Lumgair ◽  
Johnathan Reiner ◽  
Laura Marelli ◽  
Martyn Caplin ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Survival Rates ◽  
Treatment Algorithm ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Large Cell ◽  
Diagnostic Features ◽  
Free Survival ◽  
Histopathological Classification

e17543 Background: Bronchial neuroendocrine tumours, represent 1–3% of all primary lung tumours and 25% of all neuroendocrine tumours (NETs). They are classified into: typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell lung carcinomas (SCLC). The aim of our study was to assess diagnostic features, management and outcome, focusing on the differences between TC and AC. Methods: 116 patients were identified from our NET database. WHO histopathological classification was used. Follow-up was complete in all patients (mean follow-up 59.8 months). Disease-free survival (DFS), and progression-free survival (PFS) were evaluated for each therapy. Results: The average age of presentation was 55.30 years (range 16-85 years, M:F ratio=1:1.5). The commonest presenting symptom was cough (19%) followed by haemoptysis (18%). 36% were TC, 45% AC, and 19% LCNEC/SCLC. 16% TC and 28% AC patients had metastases at diagnosis. Octreoscan was positive in 76% TC and 66% AC. In 2 patients with TC and negative Octreoscan, Ga-68 Octreotate PET showed avid uptake in lung lesions. 46 patients had surgery. In 35 of AC, the disease relapsed (DFS=29.8 months) compared to 24% TC (DFS=48months). 12 patients received somatostatin analogues (SSTA) with PFS for TC 60 months and AC 21 months. 16 patients received systemic chemotherapy with PFS for TC 72 months and AC 21 months. 4/5 patients achieved disease stability with 90Yttrium-DOTAoctreotate. 5-years survival after surgery, chemotherapy or SSTA, was 91%, 86% and 81% respectively. Overall five year survival was 91% (100 % TC, 75% AC). Conclusions: AC and SCLC/LCLC more often present with metastatic disease with shorter DFS and PFS compared to TC. Molecular imaging is helpful for staging and predicting appropriateness for SSTA or radionuclide targeted therapy. Surgery confers the best survival rates. AC have higher relapse rates and metastatic potential. Further clinical trials are required to define the best treatment algorithm.

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