A Phase II Trial of Vandetanib in Children and Adults with Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor
©2019 American Association for Cancer Research..
PURPOSE: Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiotherapy. Most GIST in children are wild-type for KIT and PDGFRA (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.
PATIENTS AND METHODS: Phase II study of vandetanib (300 mg orally once daily to patients ≥18 years, and 100 mg/m2/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.
RESULTS: 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 (<18 years old) enrolled did not experience treatment-modifying toxicities. No partial or complete responses were observed (median number of cycles, 4; range, 2-18).
CONCLUSIONS: Vandetanib at a dose of 300 mg daily was not well tolerated by adults with dSDH GIST. Two of 9 patients had prolonged stable disease, but no partial or complete responses were observed, and vandetanib is thus not considered active in dSDH GIST.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 25(2019), 21 vom: 01. Nov., Seite 6302-6308 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Glod, John [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.09.2020 Date Revised 25.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-19-0986 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Glod, John |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Phase II Trial of Vandetanib in Children and Adults with Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 08.09.2020 | ||
| 500 | |a Date Revised 25.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2019 American Association for Cancer Research. | ||
| 520 | |a PURPOSE: Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiotherapy. Most GIST in children are wild-type for KIT and PDGFRA (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 | ||
| 520 | |a PATIENTS AND METHODS: Phase II study of vandetanib (300 mg orally once daily to patients ≥18 years, and 100 mg/m2/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 | ||
| 520 | |a RESULTS: 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 (<18 years old) enrolled did not experience treatment-modifying toxicities. No partial or complete responses were observed (median number of cycles, 4; range, 2-18) | ||
| 520 | |a CONCLUSIONS: Vandetanib at a dose of 300 mg daily was not well tolerated by adults with dSDH GIST. Two of 9 patients had prolonged stable disease, but no partial or complete responses were observed, and vandetanib is thus not considered active in dSDH GIST | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, N.I.H., Intramural | |
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| 700 | 1 | |a Arnaldez, Fernanda I |e verfasserin |4 aut | |
| 700 | 1 | |a Wiener, Lori |e verfasserin |4 aut | |
| 700 | 1 | |a Spencer, Melissa |e verfasserin |4 aut | |
| 700 | 1 | |a Killian, J Keith |e verfasserin |4 aut | |
| 700 | 1 | |a Meltzer, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Dombi, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Derse-Anthony, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Derdak, Joanne |e verfasserin |4 aut | |
| 700 | 1 | |a Srinivasan, Ramaprasad |e verfasserin |4 aut | |
| 700 | 1 | |a Linehan, W Marston |e verfasserin |4 aut | |
| 700 | 1 | |a Miettinen, Markku |e verfasserin |4 aut | |
| 700 | 1 | |a Steinberg, Seth M |e verfasserin |4 aut | |
| 700 | 1 | |a Helman, Lee |e verfasserin |4 aut | |
| 700 | 1 | |a Widemann, Brigitte C |e verfasserin |4 aut | |
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