Einzeltreffer — DigiBib

Background: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma.

Materials and Methods: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM).

Results: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected.

Conclusions: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.

Titel:	A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer.
Autor/in / Beteiligte Person:	O'Neil, BH ; Scott, AJ ; Ma, WW ; Cohen, SJ ; Aisner, DL ; Menter, AR ; Tejani, MA ; Cho, JK ; Granfortuna, J ; Coveler, L ; Olowokure, OO ; Baranda, JC ; Cusnir, M ; Phillip, P ; Boles, J ; Nazemzadeh, R ; Rarick, M ; Cohen, DJ ; Radford, J ; Fehrenbacher, L ; Bajaj, R ; Bathini, V ; Fanta, P ; Berlin, J ; McRee, AJ ; Maguire, R ; Wilhelm, F ; Maniar, M ; Jimeno, A ; Gomes, CL ; Messersmith, WA
Link:	Full Text Finder (Volltext)
Zeitschrift:	Annals of oncology : official journal of the European Society for Medical Oncology, Jg. 26 (2015-09-01), Heft 9, S. 1923-1929
Veröffentlichung:	2020- : London : Elsevier ; <i>Original Publication</i>: Dordrecht ; Boston : Kluwer Academic Publishers, c1990-, 2015
Medientyp:	academicJournal
ISSN:	1569-8041 (electronic)
DOI:	10.1093/annonc/mdv264
Schlagwort:	Adult Aged Aged, 80 and over Antimetabolites, Antineoplastic therapeutic use Cell Cycle Proteins antagonists & inhibitors Class I Phosphatidylinositol 3-Kinases Deoxycytidine adverse effects Deoxycytidine therapeutic use Disease-Free Survival Drug Administration Schedule Female Glycine adverse effects Glycine therapeutic use Humans Male Middle Aged Phosphatidylinositol 3-Kinases genetics Phosphoinositide-3 Kinase Inhibitors Protein Serine-Threonine Kinases antagonists & inhibitors Proto-Oncogene Proteins antagonists & inhibitors Proto-Oncogene Proteins p21(ras) genetics Sulfones adverse effects Tumor Suppressor Protein p53 genetics Gemcitabine Polo-Like Kinase 1 Pancreatic Neoplasms Adenocarcinoma drug therapy Antineoplastic Combined Chemotherapy Protocols therapeutic use Deoxycytidine analogs & derivatives Glycine analogs & derivatives Pancreatic Neoplasms drug therapy Sulfones therapeutic use
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Clinical Trial, Phase II; Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Ann Oncol] 2015 Sep; Vol. 26 (9), pp. 1923-1929. <i>Date of Electronic Publication: </i>2015 Jun 19. MeSH Terms: Adenocarcinoma / drug therapy ; Antineoplastic Combined Chemotherapy Protocols / therapeutic use ; Deoxycytidine / analogs & derivatives ; Glycine / analogs & derivatives ; Pancreatic Neoplasms / drug therapy ; Sulfones / therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic / therapeutic use ; Cell Cycle Proteins / antagonists & inhibitors ; Class I Phosphatidylinositol 3-Kinases ; Deoxycytidine / adverse effects ; Deoxycytidine / therapeutic use ; Disease-Free Survival ; Drug Administration Schedule ; Female ; Glycine / adverse effects ; Glycine / therapeutic use ; Humans ; Male ; Middle Aged ; Phosphatidylinositol 3-Kinases / genetics ; Phosphoinositide-3 Kinase Inhibitors ; Protein Serine-Threonine Kinases / antagonists & inhibitors ; Proto-Oncogene Proteins / antagonists & inhibitors ; Proto-Oncogene Proteins p21(ras) / genetics ; Sulfones / adverse effects ; Tumor Suppressor Protein p53 / genetics ; Gemcitabine ; Polo-Like Kinase 1 ; Pancreatic Neoplasms Comments: Erratum in: Ann Oncol. 2015 Dec;26(12):2505. Leichman, L [added]. (PMID: 26489442) ; Erratum in: Ann Oncol. 2016 Jun;27(6):1180. (PMID: 26945010) References: Cancer Cell. 2009 Jun 2;15(6):489-500. (PMID: 19477428) ; Onco Targets Ther. 2014 Feb 04;7:187-92. (PMID: 24523592) ; Cancer Sci. 2015 Mar;106(3):287-93. (PMID: 25580850) ; J Clin Oncol. 2007 May 20;25(15):1960-6. (PMID: 17452677) ; Clin Cancer Res. 2012 Apr 1;18(7):2048-55. (PMID: 22338014) ; Expert Opin Investig Drugs. 2011 Apr;20(4):507-18. (PMID: 21395485) ; Nat Med. 2011 Apr;17(4):500-3. (PMID: 21460848) ; Oncogene. 2005 Apr 18;24(17):2844-59. (PMID: 15838519) ; Br J Haematol. 2013 Aug;162(4):517-24. (PMID: 23789936) ; J Clin Oncol. 1997 Jun;15(6):2403-13. (PMID: 9196156) ; Lancet. 2004 Mar 27;363(9414):1049-57. (PMID: 15051286) ; Mol Cancer Ther. 2010 Feb;9(2):311-8. (PMID: 20103597) ; Science. 2008 Sep 26;321(5897):1801-6. (PMID: 18772397) ; Oncogene. 2009 Jan 29;28(4):610-8. (PMID: 19029951) ; N Engl J Med. 2011 May 12;364(19):1817-25. (PMID: 21561347) ; Hematol Oncol. 2015 Jun;33(2):57-66. (PMID: 24777753) ; Mol Cancer Ther. 2004 May;3(5):641-6. (PMID: 15141022) ; Br J Cancer. 2014 Aug 26;111(5):817-22. (PMID: 24755884) ; J Clin Oncol. 2008 Dec 1;26(34):5504-10. (PMID: 18955447) Grant Information: P30 CA016056 United States CA NCI NIH HHS Contributed Indexing: Keywords: PI3K inhibitor; PLK1 inhibitor; Ras mimetic; pancreatic cancer; phase II/III; rigosertib Substance Nomenclature: 0 (Antimetabolites, Antineoplastic) ; 0 (Cell Cycle Proteins) ; 0 (KRAS protein, human) ; 0 (Phosphoinositide-3 Kinase Inhibitors) ; 0 (Proto-Oncogene Proteins) ; 0 (Sulfones) ; 0 (TP53 protein, human) ; 0 (Tumor Suppressor Protein p53) ; 0W860991D6 (Deoxycytidine) ; 67DOW7F9GL (ON 01910) ; EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) ; EC 2.7.1.137 (PIK3CA protein, human) ; EC 2.7.11.1 (Protein Serine-Threonine Kinases) ; EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) ; TE7660XO1C (Glycine) ; 0 (Gemcitabine) Entry Date(s): Date Created: 20150621 Date Completed: 20160609 Latest Revision: 20231213 Update Code: 20240513 PubMed Central ID: PMC4551155

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer.