Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

An Overview on the Sequential Treatment of Pancreatic Neuroendocrine Tumors (pNETs)

An Overview on the Sequential Treatment of Pancreatic Neuroendocrine Tumors (pNETs) Patients suffering from pancreatic neuroendocrine tumors (pNETs) are now candidates to receive novel approved drugs that have demonstrated benefit in disease control rate and delay the time taken for tumor progression in Phase III clinical trials; for example, sunitinib, everolimus and lanreotide. Though pNETs represent a rare and heterogeneous disease, recent approaches are being taken to better understand the molecular pathways involved in carcinogenesis. Consequently, new treatment strategies are now available and others still under investigation show promising results. However, some questions around how to approach patients with pNETs are still unresolved, such as what the best sequence of treatments we can offer to each of our patients in the clinic at any time of their disease would be. Therapeutic decisions are, at the moment, guided by clinical judgment, based on different parameters coming from retrospective analysis and non-randomized clinical trials. However, advances in genomic research would lead to a more precise approach using therapeutic targets that would also allow the development of new agents, prognostic or predictive biomarkers and a better understanding of resistance mechanisms. The following article is a comprehensive review of the approved and investigational drugs in pNET, and highlights the current concerns about treatment sequencing, but also provides an update of some of the present and future efforts for an improvement in the therapeutic algorithm of the disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Oncology and Therapy Springer Journals

An Overview on the Sequential Treatment of Pancreatic Neuroendocrine Tumors (pNETs)

Download PDF
21 pages

Loading next page...
 
/lp/springer-journals/an-overview-on-the-sequential-treatment-of-pancreatic-neuroendocrine-BCnnrsiIJn
Publisher
Springer Journals
Copyright
Copyright © 2015 by The Author(s)
Subject
Medicine & Public Health; Internal Medicine
ISSN
2366-1070
eISSN
2195-6022
DOI
10.1007/s40487-015-0007-6
Publisher site
See Article on Publisher Site

Abstract

Patients suffering from pancreatic neuroendocrine tumors (pNETs) are now candidates to receive novel approved drugs that have demonstrated benefit in disease control rate and delay the time taken for tumor progression in Phase III clinical trials; for example, sunitinib, everolimus and lanreotide. Though pNETs represent a rare and heterogeneous disease, recent approaches are being taken to better understand the molecular pathways involved in carcinogenesis. Consequently, new treatment strategies are now available and others still under investigation show promising results. However, some questions around how to approach patients with pNETs are still unresolved, such as what the best sequence of treatments we can offer to each of our patients in the clinic at any time of their disease would be. Therapeutic decisions are, at the moment, guided by clinical judgment, based on different parameters coming from retrospective analysis and non-randomized clinical trials. However, advances in genomic research would lead to a more precise approach using therapeutic targets that would also allow the development of new agents, prognostic or predictive biomarkers and a better understanding of resistance mechanisms. The following article is a comprehensive review of the approved and investigational drugs in pNET, and highlights the current concerns about treatment sequencing, but also provides an update of some of the present and future efforts for an improvement in the therapeutic algorithm of the disease.

Journal

Oncology and Therapy – Springer Journals

Published: Jul 11, 2015

References

  • Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors
    Strosberg, JR; Fisher, GA; Benson, AB
  • Translation of molecular pathways into clinical trials of neuroendocrine tumors
    Pavel, M
  • Neuroendocrine gastro-entero-pancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up
    Öberg, K; Knigge, U; Kwekkeboom, D; Perren, A
  • Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis
    Ito, T; Igarashi, H; Nakamura, K
  • SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs)
    García-Carbonero, R; Jiménez, FP; Teulé, A; Barriuso, J; Sevilla, I
  • 18F-DOPA and other radiopharmaceuticals for imaging unknown primary neuroendocrine tumors
    Schillaci, O
  • Gastroenteropancreatic high-grade neuroendocrine carcinoma
    Sorbye, H; Strosberg, J; Baudin, E; Klimstra, DS; Yao, JC
  • The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogeneous and includes both well differentiated and poorly differentiated neoplasms
    Basturk, O; Yang, Z; Tang, LH
  • Rationale for the use of somatostatin analogs as antitumor agents
    Susini, C; Buscail, L
  • Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors
    Toumpanakis, C; Caplin, ME
  • Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study
    Kvols, LK; Oberg, KE; Dorisio, TMO
  • Modes of resistance to anti-angiogenic therapy
    Bergers, G; Hanahan, D
  • Resistance to targeted therapies in pancreatic neuroendocrine tumors (PNETs): molecular basis, preclinical data, and counteracting strategies
    Tijeras-Raballand, A; Neuzillet, C; Couvelard, A
  • Overcoming resistance to tyrosine kinase inhibitors in renal cell carcinoma
    Ravaud, A; Gross-Goupil, M
  • Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis
    Chiu, CW; Nozawa, H; Hanahan, D
  • Pharmacokinetics, clinical indications, and resistance mechanisms in molecular targeted therapies in cancer
    Izar, B; Rotow, J; Gainor, J; Clark, J; Chabner, B
  • Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281
    Sun, W; Lipsitz, DS; Catalano, P; Maillard, JA; Haller, D
  • Streptozocin-doxorubicin, streptozocin-fluorouracil, or chlorozotocin in the treatment of advanced islet-cell carcinoma
    Moertel, CG; Lefkopoulo, M; Lipsitz, S; Hahn, RG; Klaassen, D
  • Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282
    Ramanthan, RK; Cnaan, A; Hahn, RG; Carbone, PP; Haller, DG
  • Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas
    Kouvaraki, MA; Ajani, JA; Hoff, P
  • International practice patterns and resource utilization in the treatment of neuroendocrine tumors
    Casciano, R; Wang, X; Stern, L
  • Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer
    Faivre, S; Delbaldo, C; Vera, K
  • Activity of sunitinib in patients with advanced neuroendocrine tumors
    Kulke, MH; Lenz, HJ; Meropol, NJ
  • Sunitinib malate for the treatment of pancreatic neuroendocrine tumors
    Raymond, E; Dahan, L; Raoul, JL
  • Molecular biology of neuroendocrine tumors: from pathways to biomarkers and targets
    Capdevila, J; Meeker, A; García-Carbonero, R
  • Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study
    Yao, JC; Phan, AT; Chang, DZ
  • Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial
    Yao, JC; Lombard-Bohas, C; Baudin, E
  • Everolimus for advanced pancreatic neuroendocrine tumors
    Yao, JC; Shah, MH; Ito, T
  • Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group
    Rinke, A; Muller, HH; Schade-Brittinger, C
  • CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors
    Caplin, ME; Pavel, M; Ćwikła, JB
  • O6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors
    Kulke, MH; Hornick, JL; Frauenhoffer, C
  • O6-methylguanine-DNA methyltransferase status in neuroendocrine tumours: prognostic relevance and association with responseto alkylating agents
    Walter, T; Brakel, B; Vercherat, C
  • Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors
    Kwekkeboom, DJ; Teunissen, JJ; Bakker, WH
  • peptide receptor radionuclide therapy with 177Lu-DOTATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience
    Delpassand, ES; Samarghandi, A; Zamanian, S
  • Treatment with the radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate: toxicity, efficacy, and survival
    Kwekkeboom, DJ; Herder, WW; Kam, BL
  • Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after (177)Lu-octreotate
    Kamp, K; Gumz, B; Feelders, RA
  • Real-world study of everolimus in advanced progressive neuroendocrine tumors
    Panzuto, F; Rinzivillo, M; Fazio, N
  • Phase I trial of pazopanib in patients with advanced cancer
    Hurwitz, HI; Dowlati, A; Saini, S
  • A quantitative analysis of kinase inhibitor selectivity
    Karaman, MW; Herrgard, S; Treiber, DK
  • Phase II study of pazopanib monotherapyin metastatic gastroenteropancreaticneuroendocrine tumours
    Ahn, HK; Choi, JY; Kim, KM
  • Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumors: a multicentre, single-group, phase 2 study
    Phan, AT; Halperin, DM; Chan, JA
  • Prospective Study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors
    Chan, JA; Stuart, K; Earle, CC
  • Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial)—a phase II non-randomised trial
    Ducreux, M; Dahan, L; Smith, D
  • Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors
    Hobday, TJ; Qin, R; Reidy-Lagunes, D
  • Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumour: a phase II studyof Spanish Neuroendocrine Tumour Group (GETNE0801)
    Castellano, D; Capdevila, J; Sastre, J
  • Brivanib: a review of development
    Chou, T; Finn, RS
  • Brivanib, a dual FGF/VEGF Inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition
    Allen, E; Walters, IB; Hanahan, D
  • Differential contribution to neuroendocrine tumorigenesis of parallel egfr signaling in cancer cells and pericytes
    Nolan-Stevaux, O; Truitt, MC; Pahler, JC
  • Phase II Study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors
    Kulke, MH; Stuart, K; Enzinger, PC
  • Depletion of O6 methylguanine DNA methyltransferase by O6 benzylguanine enhances 5FU cytotoxicity in colon and oral cancer cell lines
    Murakami, J; Lee, YJ; Kokeguchi, S
  • Sequencing and combining systemic therapies for pancreatic neuroendocrine tumors
    Kulke, MH
  • First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas
    Strosberg, JR; Fine, RL; Choi, J
  • Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience
    Fine, RL; Gulati, AP; Krantz, BA; Moss, RA; Schreibman, S; Tsushima, DA
  • Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy
    Welin, S; Sorbye, H; Sebjornsen, S
  • A prospective, phase 1/2 study of everolimus and temozolomide in patients with advanced pancreatic neuroendocrine tumor
    Chan, JA; Blaszkowsky, L; Stuart, K
  • Current understanding of the molecular biology of pancreatic neuroendocrine tumors
    Zhang, J; Francois, R; Iyer, R; Seshadri, M; Zajac-Kaye, M; Hochwald, SN