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Tytuł pozycji:

A phase 1 trial of everolimus and bevacizumab in children with recurrent solid tumors.

Tytuł:
A phase 1 trial of everolimus and bevacizumab in children with recurrent solid tumors.
Autorzy:
Santana VM; Department of Oncology, St. Jude Children's Research Hospital and Comprehensive Cancer Center, Memphis, Tennessee.
Sahr N; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Tatevossian RG; Diagnostic Biomarkers Shared Resource, Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Jia S; Diagnostic Biomarkers Shared Resource, Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Campagne O; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
Sykes A; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Stewart CF; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
Furman WL; Department of Oncology, St. Jude Children's Research Hospital and Comprehensive Cancer Center, Memphis, Tennessee.
McGregor LM; Department of Pediatrics, Penn State University College of Medicine, Hershey, Pennsylvania.
Źródło:
Cancer [Cancer] 2020 Apr 15; Vol. 126 (8), pp. 1749-1757. Date of Electronic Publication: 2020 Jan 22.
Typ publikacji:
Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: <2005- >: Hoboken, NJ : Wiley
Original Publication: New York [etc.] Published for the American Cancer Society by J. Wiley [etc.]
MeSH Terms:
Angiogenesis Inhibitors/*therapeutic use
Antineoplastic Agents/*therapeutic use
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Bevacizumab/*therapeutic use
Everolimus/*therapeutic use
Neoplasm Recurrence, Local/*drug therapy
Neoplasms/*drug therapy
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Maximum Tolerated Dose ; Neoplasm Recurrence, Local/pathology ; Neoplasms/pathology ; Prognosis ; Progression-Free Survival
References:
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Grant Information:
P30 CA021765 United States CA NCI NIH HHS
Contributed Indexing:
Keywords: bevacizumab; clinical oncology; everolimus; pediatrics
Molecular Sequence:
ClinicalTrials.gov NCT00756340
Substance Nomenclature:
0 (Angiogenesis Inhibitors)
0 (Antineoplastic Agents)
2S9ZZM9Q9V (Bevacizumab)
9HW64Q8G6G (Everolimus)
Entry Date(s):
Date Created: 20200123 Date Completed: 20201110 Latest Revision: 20210415
Update Code:
20240104
PubMed Central ID:
PMC7103504
DOI:
10.1002/cncr.32722
PMID:
31967673
Czasopismo naukowe
Background: The prognosis for children with recurrent solid tumors generally is poor. Targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor A with everolimus and bevacizumab, respectively, synergistically improves progression-free survival and is well tolerated in adults with solid tumors.
Methods: In the current phase 1 study, a total of 15 children with recurrent or refractory solid tumors were treated with bevacizumab and everolimus to establish the maximum tolerated dose, toxicity, and preliminary antitumor response (ClinicalTrials.gov identifier NCT00756340). The authors also evaluated everolimus-mediated inhibition of the mTOR pathway in the peripheral blood mononuclear cells of treated patients.
Results: Tumors predominantly were soft tissue and/or bone sarcomas (8 cases) and brain tumors (5 cases). The first 2 patients enrolled at dose level 1 (10 mg/kg of bevacizumab and 4 mg/m 2 of everolimus) experienced dose-limiting toxicities (DLTs). The next 5 patients were enrolled at dose level 0 (8 mg/kg of bevacizumab and 4 mg/m 2 of everolimus), and DLTs occurred in 2 patients. The authors then modified the protocol to permit expansion of dose 0, and 8 additional patients were added, with no DLTs reported. Of all the patients, stable disease occurred in 4 patients (30.8%; median, 2 courses), and progressive disease occurred in 9 patients (69.2%). Overall survival was 0.59 years (95% CI, 0.24-1.05 years). The mTOR biomarker phospho-4EBP1 Thr/37/46 significantly decreased from baseline to day 27 in peripheral blood mononuclear cells (P = .045). Phospho-AKT levels also decreased from those at baseline.
Conclusions: The maximum tolerated dose of cotreatment with bevacizumab and everolimus was 8 mg/kg of bevacizumab and 4 mg/m 2 of everolimus in a 4-week cycle for children with recurrent solid tumors.
(© 2020 American Cancer Society.)

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