Abstract | PURPOSE: PATIENTS AND METHODS:
Radiotherapy was administered as 1.8-Gy fractions (total cumulative dose of 54 Gy). Vandetanib was administered concurrently with radiotherapy for a maximum of 2 years. Dose-limiting toxicities (DLTs) were evaluated during the first 6 weeks of therapy. Pharmacokinetic studies were obtained for all patients. Plasma angiogenic factors and VEGFR2 phosphorylation in mononuclear cells were analyzed before and during therapy. RESULTS: Twenty-one patients were administered 50 (n = 3), 65 (n = 3), 85 (n = 3), 110 (n = 6), and 145 mg/m(2) (n = 6) of vandetanib. Only one patient developed DLT (grade 3 diarrhea) at dosage level 5. An expanded cohort of patients were treated at dosage levels 4 (n = 10) and 5 (n = 4); two patients developed grade 4 hypertension and posterior reversible encephalopathy syndrome while also receiving high-dose dexamethasone. Despite significant interpatient variability, exposure to vandetanib increased with higher dosage levels. The bivariable analysis of vascular endothelial growth factor ( VEGF) before and during therapy showed that patients with higher levels of VEGF before therapy had a longer progression-free survival (PFS; P = .022), whereas patients with increases in VEGF during treatment had a shorter PFS (P = .0015). VEGFR2 phosphorylation was inhibited on day 8 or 29 of therapy compared with baseline (P = .039). CONCLUSION:
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Authors | Alberto Broniscer, Justin N Baker, Michael Tagen, Arzu Onar-Thomas, Richard J Gilbertson, Andrew M Davidoff, Atmaram S Pai Panandiker, Atmaram Pai Panandiker, Wing Leung, Thomas K Chin, Clinton F Stewart, Mehmet Kocak, Christopher Rowland, Thomas E Merchant, Sue C Kaste, Amar Gajjar |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 28
Issue 31
Pg. 4762-8
(Nov 01 2010)
ISSN: 1527-7755 [Electronic] United States |
PMID | 20921456
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Piperidines
- Quinazolines
- vandetanib
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Topics |
- Adolescent
- Antineoplastic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Brain Stem Neoplasms
(diagnosis, drug therapy, radiotherapy)
- Chemotherapy, Adjuvant
- Child
- Child, Preschool
- Disease-Free Survival
- Dose Fractionation, Radiation
- Drug Administration Schedule
- Female
- Glioma
(diagnosis, drug therapy, radiotherapy)
- Humans
- Kaplan-Meier Estimate
- Magnetic Resonance Imaging
- Male
- Maximum Tolerated Dose
- Piperidines
(administration & dosage, adverse effects, pharmacokinetics)
- Quinazolines
(administration & dosage, adverse effects, pharmacokinetics)
- Radiotherapy, Adjuvant
- Treatment Outcome
- Young Adult
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