Background and Aim Chemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as impartial risk factors for shorter PFS. Additionally, overall performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities. Conclusions STZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response. Introduction Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with increasing incidence [1] originating from endocrine cells in different anatomic locations. Pancreatic NETs differ AR-42 from intestinal NETs in many aspects including clinical presentation with unique hormone syndromes, genetic findings (e.g. mutations in the Menin gene [2]), a more aggressive course of disease resulting in worse prognosis [1], and responsiveness to treatment modalities such as molecular targeted brokers and chemotherapy. While the results of chemotherapy in patients with intestinal NETs are disappointing resulting in objective response rates of less than 20% in most trials, pancreatic NETs were shown to be chemosensitive. The combination of streptozocin (STZ) and fluorouracil (5-FU) is recommended as standard treatment for metastatic pancreatic AR-42 NETs in European guidelines [3, 4]. STZ is available since the early 80ies and approved for the treatment of pancreatic NETs in several countries. The early prospective randomized trials by Moertel reported high response rates (RR) of STZ-based combinations exceeding 60% [5, 6]. However, two subsequent retrospective series failed to confirm these results, which was attributed the definition of response [7, 8]. More recently, larger retrospective studies using standardized radiological response criteria repeatedly reported RRs ranging between 30 and 40% for STZ-based combination treatments [9C11]. A variety of prognostic factors has been described for patients with NETs including age, performance status, stage according to ENETS [12, 13] and AJCC [14], tumor load, levels of chromogranin A (CgA) [15], presence of circulating tumor cells [16] and grading based on the proliferation marker Ki-67. The latest WHO classification [17] of NETs is based on Ki-67 values and the prognostic relevance of this grading system has been validated in several studies [12, 18C20]. In contrast, the predictive value of Ki-67 is usually less clear. To date, no established predictive markers are available to facilitate treatment decisions. The ESMO guideline recommends the use of STZ-based chemotherapy in patients with pancreatic NETs and a proliferation rate between 5 and 20% [4]. However, this represents an expert opinion which is not evidence-based, since most chemotherapy trials in pNEN published so far did not assess the role of Ki-67 as predictive marker. Only in one study by OToole and co-workers an association between Ki-67 levels >5% and lack of response to systemic chemotherapy was reported [21]. It was thus the aim of our study to identify prognostic and predictive markers for pNEN-patients treated with STZ-based chemotherapy at our center. Patients and Methods Patients 77 consecutive patients with histologically confirmed pancreatic neuroendocrine tumors who received STZ-based chemotherapy between 1995 and 2013 were retrospectively recognized from a database at Rabbit Polyclonal to HBP1 the comprehensive cancer center at the University or college Hospital of Marburg. This study was conducted in accordance with the Declaration of Helsinki. Collection, storage, and evaluation of patient-related information in our NEN database were performed with the approval of the local ethics committee at the University or college of Marburg and after obtaining the patients informed consent. The initial statement of the local ethics committee was that a formal approval and written informed consent for collection and analysis of data arising from the routine clinical evaluation within the own hospital was not required. Therefore, patients who experienced their last visit/ died before 2004 only were asked for verbal consent (with approval of the ethics committee of this consent process). In 2004 the German NET registry was built up and for transmission of pseudonymized data a written AR-42 approval of the ethics committee was obtained. Since then all patients additionally gave a written consent for data collection and analysis. Protocol treatment and toxicity assessment All patients received STZ-containing chemotherapy in combination with Doxorubicin (Dox) or 5-FU. For patients who in the beginning received chemotherapy with STZ/Dox, Dox was replaced by 5-FU before the cumulative cardiotoxic dose of 550mg/m2 Dox AR-42 was reached. The chemotherapeutic STZ/Dox regimen included STZ at a dose of 500 mg/m2 on day 1C5 and Dox at a dose of 50 mg/m2 on day 1 and 22. The regimen was repeated.
Tag Archives: Rabbit Polyclonal to HBP1
Categories
- 34
- 5- Receptors
- A2A Receptors
- ACE
- Acetylcholinesterase
- Adenosine Deaminase
- Adenylyl Cyclase
- Adrenergic ??2 Receptors
- Alpha2 Adrenergic Receptors
- Annexin
- Antibiotics
- ATPase
- AXOR12 Receptor
- Ca2+ Ionophore
- Cannabinoid
- Cannabinoid (GPR55) Receptors
- CB2 Receptors
- CCK Receptors
- Cell Metabolism
- Cell Signaling
- Cholecystokinin2 Receptors
- CK1
- Corticotropin-Releasing Factor1 Receptors
- DHCR
- DMTases
- DNA Ligases
- DNA Methyltransferases
- Dopamine D1 Receptors
- Dopamine D3 Receptors
- Dopamine D4 Receptors
- Endothelin Receptors
- EP1-4 Receptors
- Epigenetics
- Exocytosis & Endocytosis
- Fatty Acid Synthase
- Flt Receptors
- GABAB Receptors
- GIP Receptor
- Glutamate (Kainate) Receptors
- Glutamate (Metabotropic) Group III Receptors
- Glutamate (NMDA) Receptors
- Glutamate Carboxypeptidase II
- Glycogen Phosphorylase
- Glycosyltransferase
- GnRH Receptors
- Heat Shock Protein 90
- hERG Channels
- Hormone-sensitive Lipase
- IKK
- Imidazoline Receptors
- IMPase
- Inositol Phosphatases
- Kisspeptin Receptor
- LTA4 Hydrolase
- M1 Receptors
- Matrixins
- Melastatin Receptors
- mGlu Group III Receptors
- mGlu5 Receptors
- Monoamine Oxidase
- Motilin Receptor
- My Blog
- Neutrophil Elastase
- Nicotinic (??4??2) Receptors
- NKCC Cotransporter
- NMU Receptors
- Nociceptin Receptors
- Non-Selective
- Non-selective 5-HT
- OP3 Receptors
- Opioid, ??-
- Orexin2 Receptors
- Other
- Other Oxygenases/Oxidases
- Other Transcription Factors
- p38 MAPK
- p53
- p56lck
- PAF Receptors
- PDPK1
- PKC
- PLA
- PPAR
- PPAR??
- Proteasome
- PTH Receptors
- Ras
- RNA Polymerase
- Serotonin (5-HT2B) Receptors
- Serotonin Transporters
- Sigma2 Receptors
- Sodium Channels
- Steroid Hormone Receptors
- Tachykinin NK1 Receptors
- Tachykinin NK2 Receptors
- Tachykinin, Non-Selective
- Telomerase
- Thyrotropin-Releasing Hormone Receptors
- Topoisomerase
- trpp
- Uncategorized
- USP
Recent Posts
- 2012) using the Phenotypic Characteristic Search for human strains with markers for resistance to Adamantane, Oseltamivir, or both drugs
- Tissue were homogenized into single-cell suspensions and put through red bloodstream cell lysis
- A phase I/II study investigated the safety and efficacy of concurrent local palliative RT and durvalumab (PD-L1 inhibitor) in 10 patients with unresectable or metastatic advanced solid tumors [136]
- We believe that this hypothesis-generating study could open new avenues for exploring oxidative stress as a potential pathogenetic and, hypothetically, therapeutic target for mitigating CLL strong class=”kwd-title” Keywords: Leukemia, Lymphocytic, Gilbert’s, Syndrome Gilbert’s syndrome (GS) is the most common inherited disorder of bilirubin glucuronidation
- Such costs aren’t simple for tertiary-care hospitals in growing countries sometimes, since these already are powered by minimal budget which switches into provision of fundamental medical services mostly, laboratory, radiology, pharmacy services, and bed space
Tags
a 67 kDa type I transmembrane glycoprotein present on myeloid progenitors
and differentiation. The protein kinase family is one of the largest families of proteins in eukaryotes
Apoptosis
bladder
brain
breast
cell cycle progression
cervix
CSP-B
Cyproterone acetate
EGFR) is the prototype member of the type 1 receptor tyrosine kinases. EGFR overexpression in tumors indicates poor prognosis and is observed in tumors of the head and neck
EM9
endometrium
erythrocytes
F3
Goat polyclonal to IgG H+L)
Goat polyclonal to IgG H+L)Biotin)
GRK4
GSK1904529A
Igf1
Mapkap1
monocytes andgranulocytes. CD33 is absent on lymphocytes
Mouse monoclonal to CD33.CT65 reacts with CD33 andtigen
Palomid 529
platelets
PTK) or serine/threonine
Rabbit Polyclonal to ARNT.
Rabbit polyclonal to BMPR2
Rabbit Polyclonal to CCBP2.
Rabbit Polyclonal to EDG4
Rabbit polyclonal to EIF4E.
Rabbit polyclonal to IL11RA
Rabbit polyclonal to LRRIQ3
Rabbit Polyclonal to MCM3 phospho-Thr722)
Rabbit Polyclonal to RBM34
SB 216763
SKI-606
SNX-5422
STK) kinase catalytic domains. Epidermal Growth factor receptor
stomach
stomach and in squamous cell carcinoma.
TNFSF8
TSHR
VEGFA
vulva