Abstract:
BACKGROUND:We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. METHODS:Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of "long responder" patients and of time to progression (TTP) and overall survival (OS) at 5 years. RESULTS:Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). CONCLUSION:In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term.
journal_name
Neuroendocrinologyjournal_title
Neuroendocrinologyauthors
Bajetta E,Catena L,Pusceddu S,Spada F,Iannacone C,Sarno I,Di Menna G,Dottorini L,Marte AMdoi
10.1159/000479587subject
Has Abstractpub_date
2018-01-01 00:00:00pages
307-311issue
4eissn
0028-3835issn
1423-0194pii
000479587journal_volume
106pub_type
杂志文章,多中心研究abstract::We have investigated the hypothesis that administration of progesterone to estrogen-treated ovariectomized (OVX) rats enhances the stimulatory effects of neuropeptide Y (NPY) on the secretion of luteinizing hormone-releasing hormone (LHRH) from median eminence (ME) fragments in vitro. Adult rats were bilaterally OVX a...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125651
更新日期:1990-12-01 00:00:00
abstract::It has been well documented that interleukin-1beta (IL-1beta) is a major mediator for recruiting the hypothalamo-pituitary-adrenal (HPA) axis following infectious disease. The recent localization of IL-1beta receptors in neurons of the hippocampus provides further support for the role of IL-1beta as a neurotransmitter...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054405
更新日期:1999-02-01 00:00:00
abstract::Unlike rats, but similar to primates, guinea pigs exhibit prolonged function of the corpus luteum and elevated progesterone secretion after ovulation. The gonadotropins, estrogen (E) and progesterone (P) have been examined throughout the guinea pig estrous cycle. However, neither prolactin secretion nor its regulation...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126897
更新日期:1995-06-01 00:00:00
abstract::An enriched population of cells immunoreactive to antiserum against S-100 protein, a marker of folliculo-stellate (FS) cells in the rat pituitary, was obtained by separation of dispersed pituitary cells from adult female rats by gradient sedimentation at unit gravity. The effect of FS cells on the stimulation and inhi...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125146
更新日期:1989-04-01 00:00:00
abstract::In the course of the search for the prolactin-releasing factor (PRF), we noticed that the posterior pituitary contained strong PRF activity and subsequently traced this activity to that of bovine neurophysin-II (NP-II). NP-II prepared in our lab was judged to be a homogeneous preparation according to Sephadex G-75 gel...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124190
更新日期:1985-10-01 00:00:00
abstract::The effects of acute and chronic administration of a combination of lynestrenol-mestrenol, a widely employed contraceptive medication, on the dopaminergic system of the rat forebrain and striatum were investigated to better understand the biochemical basis of the neurological side-effects of steroid contraceptive drug...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122643
更新日期:1976-01-01 00:00:00
abstract:AIM:To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features. METHODS:A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 at...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000381454
更新日期:2015-01-01 00:00:00
abstract::Thyroid hormones and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling play a significant role in the structural development of the cerebellum, respectively. In the present study, the possible contribution of neuronal NO synthase (NOS) and cGMP in the thyroid hormone-induced structural changes was invest...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000203644
更新日期:2009-01-01 00:00:00
abstract::The obese gene (OB) product, leptin, has been shown to exert control on metabolic processes such as food intake and body weight homeostasis, possibly through a neuropeptide Y (NPY) neurotransmission. More recently, leptin has been shown to control several neuroendocrine axes, modulating pituitary hormone secretions in...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054326
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND/AIMS:Both prostaglandin E2 (PGE2) and estradiol stimulate fetal ACTH secretion and augment fetal ACTH responses to stress. We have reported that estradiol increases prostaglandin endoperoxide synthase-2 (PGHS-2), and we have proposed that there is a positive feedback relationship between estrogen and fetal h...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000109664
更新日期:2008-01-01 00:00:00
abstract::Interactions between the hypothalamic-pituitary-adrenocortical (HPA) system and melatonin secretion have been demonstrated, but only the effects of melatonin on the activity of the HPA system have been studied in man. Alterations of melatonin secretion described as low-melatonin syndrome have been demonstrated in pati...
journal_title:Neuroendocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1159/000127186
更新日期:1997-04-01 00:00:00
abstract::Incubation of cultured goldfish pituitary cells with 10 nM to 1 microM apomorphine (APO), a non-selective dopamine agonist, increased growth hormone (GH) release in a dose-dependent manner. GH release was also stimulated in a dose-dependent manner by 0.1 nM to 1 microM salmon gonadotropin (GTH)-releasing hormone (sGnR...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125408
更新日期:1990-06-01 00:00:00
abstract:INTRODUCTION:Small-intestinal neuroendocrine tumors (SI-NET) are situated preferentially within the ileum. The aim was to describe a potential difference in location between unifocal and multiple ileal-NET. METHODS:Between December 2010 and December 2019, all consecutive patients who underwent resection in our Europea...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000511849
更新日期:2020-09-30 00:00:00
abstract::Hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HG rat) for 3 weeks with or without estradiol implantation, were used to examine prolactin (PRL) secretion independent of hypothalamic influence. Changes in the circulating PRL concentration were monitored by taking blood samples every ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123146
更新日期:1981-03-01 00:00:00
abstract::The A1 and A2 brainstem noradrenergic cell groups project to the hypothalamic paraventricular nucleus (PVN), which is involved in integrating the stress response. Bi-directional communication between the brain and immune system is well established, with both neuroendocrine and immune responses being activated by lipop...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054474
更新日期:1999-09-01 00:00:00
abstract::The release of endogenous noradrenaline in the anterior hypothalamus was studied with microdialysis perfusion in freely moving rats that were subjected to immobilization stress. Experiments were carried out in sham-adrenalectomized and adrenalectomized rats that were first given drinking water containing corticosteron...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126442
更新日期:1993-05-01 00:00:00
abstract::17 alpha-hydroxyprogesterone (up to 200 mug/day) and 11 beta-hydroxyandrostenedione (up to 500 mug) had no effect on PMS-induced ovulation in intact immature rats. 10 mug/day of testosterone propoinate (TP) on days 28-30 of life decreased the percent of animals ovulating and the number of ova produced; this effect per...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122338
更新日期:1975-01-01 00:00:00
abstract::The parenchymal cells of the pars intermedia (PI) and corticotrophs of the pars distalis (PD) synthesize pro-opiomelanocortin (POMC), which, through posttranslational processing, gives rise to a group of structurally related peptides, including MSHs, ACTH, CLIP, LPHs and endorphins. We investigated the control of rele...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124203
更新日期:1985-11-01 00:00:00
abstract::The distribution of gamma-aminobutyric acid (GABA) nerve fibers and cell bodies in the rat hypothalamus and pituitary gland was immunohistochemically examined using antibodies against the GABA-synthesizing enzyme glutamate decarboxylase (GAD). The dense network of GAD-positive nerve fibers was observed to be essential...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123288
更新日期:1982-02-01 00:00:00
abstract::The aim of this study was to examine the occurrence of endogenous oscillations of Per1, Per2, Bmal1 and Rev-erbα genes in rat pineal explants and to investigate their regulation by adrenergic ligands. Our results show a significant and sustained rhythm of Per2,Bmal1 and Rev-erbα gene expression for up to 48 h in cultu...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000327430
更新日期:2011-01-01 00:00:00
abstract::The hypothalamic preoptic area (POA) was electrically stimulated through permanently implanted electrodes in 4 unanesthetized sheep. Initiation of POA stimulation was followed witin 10-20 min by large increases in plasma levels of prolactin (PRL). The stimulation-induced discharges of PRL were consistently observed in...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122384
更新日期:1975-01-01 00:00:00
abstract::Many aspects of reproductive neuroendocrine function and sexual behavior are responsive to both androgens and estrogens, suggesting that receptors for these steroid hormones may reside within single cells in brain regions that control reproductive function. We determined the distribution of estrogen receptor-containin...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000127039
更新日期:1995-11-01 00:00:00
abstract::It is now well documented that various polyclonal antisera to the human growth hormone-releasing factor (hGHRF, somatocrinin) visualize in the brain by immunohistochemistry the classical hypothalamic hypophysiotropic neurons and also antigens present in otherwise characterized peptidergic neuronal systems. The nature ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125370
更新日期:1990-04-01 00:00:00
abstract::Copulatory behavior in the ovariectomized rat, i.e. the lordosis response (LR) on being mounted by a male, can be induced by administration of either estrogen alone or estrogen followed by progesterone. LR has been shown to be inhibited by lysergic acid diethylamide (LSD) in certain doses (greater than or equal to 50 ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123499
更新日期:1983-06-01 00:00:00
abstract::The study was designed to determine whether the ability of central oxytocin (OT) to stimulate gonadotropin-releasing hormone (GnRH) on the afternoon of proestrus (PE) in the cycling female rat is mediated at the level of GnRH terminals within the median eminence (ME), or at higher hypothalamic levels where GnRH cell b...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054678
更新日期:2001-08-01 00:00:00
abstract::An influence of thyroid status on the secretory activity of hypothalamic dopaminergic neurons was observed in adult rats and its involvement in the regulation of prolactin (PRL) secretion was examined. The secretory activity of the tuberoinfundibular dopaminergic (TIDA) neurons was evaluated by measurement of dopamine...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124797
更新日期:1987-06-01 00:00:00
abstract::The aim of this study was to verify whether prolonged exposure of cultured rat anterior pituitary cells to high glucose can alter growth hormone (GH) release and responsiveness to secretagogues. Therefore, we cultured anterior pituitary cells obtained from normal male Sprague-Dawley rats in presence of normal (6 mM) o...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125947
更新日期:1991-11-01 00:00:00
abstract::The effect of stress- or lipopolysaccharide (LPS) endotoxin-induced release of ACTH, beta-endorphin (beta-END) and prolactin (PRL) was investigated in two groups of conscious male rats: (1) Rats pretreated with different H3 receptor agonists, which inhibit neuronal histamine (HA) synthesis and release, and (2) rats wi...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054402
更新日期:1999-01-01 00:00:00
abstract::The relationship between concentrations of vasopressin in plasma and cerebrospinal fluid (CSF) was examined under basal and hypoxic conditions in unanesthetized and unrestrained adult female sheep. Under basal conditions mean (+/- SE) concentration of vasopressin (4.1 +/- 0.3 pg/ml) in CSF was significantly (p less th...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123933
更新日期:1984-06-01 00:00:00
abstract::Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive respo...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000328226
更新日期:2011-01-01 00:00:00