A Phase II Trial of Vandetanib in Children and Adults with Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiotherapy. Most GIST in children are wild-type for and (WT GIST) and deficient in expression of succinate dehydrogenase (dSDH GIST). We tested the activity of vandetanib, an oral small-molecule inhibitor of VEGFR2,...

Full description

Saved in:
Bibliographic Details
Published in:Clinical cancer research 2019-11, Vol.25 (21), p.6302-6308
Main Authors: Glod, John, Arnaldez, Fernanda I, Wiener, Lori, Spencer, Melissa, Killian, J Keith, Meltzer, Paul, Dombi, Eva, Derse-Anthony, Claudia, Derdak, Joanne, Srinivasan, Ramaprasad, Linehan, W Marston, Miettinen, Markku, Steinberg, Seth M, Helman, Lee, Widemann, Brigitte C
Format: Article
Language:English
Subjects:
Adolescent
Adult
Child
Disease-Free Survival
Female
Gastrointestinal Stromal Tumors - drug therapy
Gastrointestinal Stromal Tumors - genetics
Gastrointestinal Stromal Tumors - pathology
Humans
Male
Middle Aged
Mutation - genetics
Neoplasm Metastasis
Piperidines - administration & dosage
Piperidines - adverse effects
Progression-Free Survival
Proto-Oncogene Proteins c-kit - genetics
Quality of Life
Quinazolines - administration & dosage
Quinazolines - adverse effects
Receptor, Platelet-Derived Growth Factor alpha - genetics
Succinate Dehydrogenase - genetics
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiotherapy. Most GIST in children are wild-type for and (WT GIST) and deficient in expression of succinate dehydrogenase (dSDH GIST). We tested the activity of vandetanib, an oral small-molecule inhibitor of VEGFR2, EGFR, and RET, in patients with dSDH GIST. Phase II study of vandetanib (300 mg orally once daily to patients ≥18 years, and 100 mg/m /dose to patients < 18 years) on a continuous dosing schedule (1 cycle = 28 days) to assess the clinical activity (partial and complete response rate RECIST v1.1) in patients with dSDH GIST. A Simon optimal two-stage design (target response rate 25%, rule out 5%) was used: If ≥1 of 9 patients in stage 1 responded, enrollment would be expanded to 24 patients, and if ≥3 of 24 responded, vandetanib would be considered active. Nine patients (7 female and 2 male; median age, 24 years; range, 11-52) with metastatic disease were enrolled. Three of the initial 5 adult patients developed treatment-modifying toxicities. After a protocol amendment, two adults received vandetanib at 200 mg/dose with improved tolerability. The two children (
ISSN:1078-0432
1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-19-0986