SFCE-RAPIRI Phase I Study of Rapamycin Plus Irinotecan: A New Way to Target Intra-Tumor Hypoxia in Pediatric Refractory Cancers.

HIF1 intra-tumor hypoxia mTor pediatric refractory cancers

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
20 Oct 2020
Historique:
received: 21 08 2020
revised: 09 10 2020
accepted: 09 10 2020
entrez: 23 10 2020
pubmed: 24 10 2020
medline: 24 10 2020
Statut: epublish

Résumé

Hypoxic environment is a prognostic factor linked in pediatric cancers to a worse outcome, favoring tumor progression and resistance to treatments. The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1 pathway can be targeted by rapamycin and irinotecan, respectively. Therefore, we designed a phase I trial associating both drugs in pediatric refractory/relapsing solid tumors. Patients were enrolled according to a 3 + 3 escalation design with ten levels, aiming to determine the MTD (maximum tolerated dose) of rapamycin plus irinotecan. Rapamycin was administered orally once daily in a 28-day cycle (1 to 2.5 mg/m

Identifiants

pubmed: 33092063
pii: cancers12103051
doi: 10.3390/cancers12103051
pmc: PMC7656302
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Institut National Du Cancer
ID : N° Eudract: 2010-022329-13

Références

J Clin Oncol. 2007 Oct 20;25(30):4722-9
pubmed: 17947719
J Neuroimaging. 2017 Jan;27(1):128-134
pubmed: 27079293
Toxicol Appl Pharmacol. 2014 Feb 1;274(3):471-9
pubmed: 24380837
Oncotarget. 2017 May 23;8(34):56698-56713
pubmed: 28915623
Oncogene. 2019 Sep;38(39):6585-6598
pubmed: 31444410
Eur J Cancer. 2012 Jan;48(2):253-62
pubmed: 22033322
Pediatr Blood Cancer. 2012 Mar;58(3):372-9
pubmed: 21509928
Nat Rev Cancer. 2004 May;4(5):335-48
pubmed: 15122205
Biochem Biophys Res Commun. 2015 Jun 5;461(3):560-7
pubmed: 25912138
J Clin Oncol. 2004 Apr 15;22(8):1382-8
pubmed: 15007088
Clin Cancer Res. 2014 Jun 15;20(12):3133-45
pubmed: 24727322
Clin Cancer Res. 2007 Apr 15;13(8):2441-8
pubmed: 17438103
Clin Pharmacokinet. 2018 Oct;57(10):1229-1254
pubmed: 29520731
J Clin Oncol. 2007 Oct 20;25(30):4806-12
pubmed: 17947729
Cell Tissue Res. 2018 May;372(2):269-275
pubmed: 29032465
Cancer Chemother Pharmacol. 2008 Nov;62(6):1027-37
pubmed: 18278496
Clin Cancer Res. 2013 Jul 1;19(13):3649-58
pubmed: 23659969
Cancer Metab. 2014 Feb 04;2(1):3
pubmed: 24491179
Cancer Res. 2006 Apr 15;66(8):4249-55
pubmed: 16618748
Cancer Res. 2005 Aug 15;65(16):7267-75
pubmed: 16103078
Pediatr Blood Cancer. 2006 Jan;46(1):50-5
pubmed: 15768380
Lancet Oncol. 2017 Jul;18(7):946-957
pubmed: 28549783
J Clin Oncol. 2011 Jul 20;29(21):2933-40
pubmed: 21690471
Oncologist. 2012;17(8):1063-72
pubmed: 22707516
Pediatr Blood Cancer. 2019 Mar;66(3):e27540
pubmed: 30393943
Science. 2009 May 22;324(5930):1029-33
pubmed: 19460998
Pediatr Blood Cancer. 2015 Mar;62(3):440-4
pubmed: 25446280
Br J Cancer. 2003 Jun 16;88(12):1925-31
pubmed: 12799638
Oral Oncol. 2018 Feb;77:9-15
pubmed: 29362130
Cancer Res. 2000 Dec 15;60(24):6921-6
pubmed: 11156391
J Neurooncol. 2010 Sep;99(2):177-85
pubmed: 20066473
Acta Radiol. 2020 Jun 15;:284185120933219
pubmed: 32539423
Clin Orthop Relat Res. 2008 Sep;466(9):2052-9
pubmed: 18528739
Pediatr Blood Cancer. 2008 Apr;50(4):799-805
pubmed: 17635004
Nat Rev Cancer. 2011 Feb;11(2):85-95
pubmed: 21258394
Cancer Res. 2009 Mar 15;69(6):2663-8
pubmed: 19276368
Clin Pharmacol Ther. 1999 May;65(5):576-82
pubmed: 10340924
World J Gastroenterol. 2009 Sep 14;15(34):4278-83
pubmed: 19750570
Lancet Oncol. 2015 Jun;16(6):e270-8
pubmed: 26065612
Clin Radiol. 2015 Oct;70(10):1087-95
pubmed: 26231469
J Biol Chem. 2007 Jul 13;282(28):20534-43
pubmed: 17502379
J Clin Pharmacol. 2015 Nov;55(11):1303-12
pubmed: 25975718
Mol Cancer Ther. 2010 Jun;9(6):1755-63
pubmed: 20530716
Mol Med. 2012 Feb 10;18:83-94
pubmed: 22033674
Clin Cancer Res. 2009 Feb 15;15(4):1297-307
pubmed: 19190131
Clin Cancer Res. 2017 Oct 1;23(19):5769-5778
pubmed: 28679773
Pediatr Blood Cancer. 2014 May;61(5):833-9
pubmed: 24249672
J Clin Neurosci. 2006 Oct;13(8):811-7
pubmed: 16997706
Cancer Lett. 2010 Sep 1;295(1):100-9
pubmed: 20356670
Acta Neuropathol. 2005 Feb;109(2):211-6
pubmed: 15614581
Trends Cancer. 2016 Dec;2(12):758-770
pubmed: 28741521
Oncotarget. 2017 Mar 23;8(42):71597-71617
pubmed: 29069732

Auteurs

Sarah Jannier (S)

Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, 67098 Strasbourg, France.

Véronique Kemmel (V)

Laboratory of Biochemistry, University Hospital of Strasbourg, 67098 Strasbourg, France.
Laboratory of Pharmacology and Toxicology in Neurocardiology-EA7296, University of Strasbourg,67000 Strasbourg, France.

Consuelo Sebastia Sancho (C)

Radiology Department, Pediatric Unit, University Hospital of Strasbourg, 67098 Strasbourg, France.

Agathe Chammas (A)

Radiology Department, Pediatric Unit, University Hospital of Strasbourg, 67098 Strasbourg, France.

Amelia-Naomie Sabo (AN)

Laboratory of Biochemistry, University Hospital of Strasbourg, 67098 Strasbourg, France.
Laboratory of Pharmacology and Toxicology in Neurocardiology-EA7296, University of Strasbourg,67000 Strasbourg, France.

Erwan Pencreach (E)

Oncobiology Platform, Laboratory of Biochemistry and Molecular Biology,University Hospital of Strasbourg, 67098 Strasbourg, France.

Françoise Farace (F)

«Circulating Tumor Cells» Translational Platform, Gustave Roussy, University of Paris-Saclay,94800 Villejuif, France.

Marie Pierre Chenard (MP)

Pathology Department, University Hospital of Strasbourg, 67098 Strasbourg, France.
Centre de Ressources Biologiques, University Hospital of Strasbourg, 67098 Strasbourg, France.

Benoit Lhermitte (B)

Pathology Department, University Hospital of Strasbourg, 67098 Strasbourg, France.

Birgit Geoerger (B)

Gustave Roussy Cancer Center, Department of Pediatric and Adolescent Oncology, Université Paris-Saclay,INSERM U1015, 94800 Villejuif, France.

Isabelle Aerts (I)

Oncology Center SIREDO, Institut Curie, PSL Research University, 75005 Paris, France.

Didier Frappaz (D)

Pediatric Oncology Department, Léon Berard Institute, 69373 Lyon, France.

Pierre Leblond (P)

Pediatric Oncology Department, Léon Berard Institute, 69373 Lyon, France.
Pediatric Oncology Unit, Oscar Lambret Center, 59020 Lille, France.

Nicolas André (N)

Pediatric Onco-Hematology Unit, CHU La Timone, 13005 Marseille, France.

Stephane Ducassou (S)

Pediatric Onco-Hematology Department, University Hospital of Bordeaux, 33000 Bordeaux, France.

Nadège Corradini (N)

Pediatric Oncology Department, Léon Berard Institute, 69373 Lyon, France.
Pediatric Oncology Unit, University Hospital of Nantes, 44093 Nantes, France.

Anne Isabelle Bertozzi (AI)

Pediatric Onco-Hematology Department, University Hospital of Toulouse, 31059 Toulouse, France.

Eric Guérin (E)

Laboratory of Biochemistry, University Hospital of Strasbourg, 67098 Strasbourg, France.

Florence Vincent (F)

Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, 67098 Strasbourg, France.

Michel Velten (M)

Clinical Research Department, ICANS, 67200 Strasbourg, France.

Natacha Entz-Werle (N)

Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, 67098 Strasbourg, France.
UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets,Faculty of Pharmacy, 67401 Illkirch, France.

Classifications MeSH