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Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Fox, Elizabeth Widemann, Brigitte C. Chuk, Meredith K. Marcus, Leigh Jessica Aikin, Alberta A. Whitcomb, Patricia O. Merino, María Teresa Martínez Lodish, Maya Dombi, Eva Steinberg, Seth M. Jr. Samuel A. Wells Balis, Frank M. |
| Copyright Year | 2013 |
| Abstract | PURPOSE Medullary thyroid carcinoma (MTC) is a manifestation of multiple endocrine neoplasia type 2 (MEN2) syndromes caused by germline, activating mutations in the RET (REarranged during Transfection) proto-oncogene. Vandetanib, a VEGF and EGF receptor inhibitor, blocks RET tyrosine kinase activity and is active in adults with hereditary MTC. EXPERIMENTAL DESIGN We conducted a phase I/II trial of vandetanib for children (5-12 years) and adolescents (13-18 years) with MTC to define a recommended dose and assess antitumor activity. The starting dose was 100 mg/m(2) administered orally, once daily, continuously for 28-day treatment cycles. The dose could be escalated to 150 mg/m(2)/d after two cycles. Radiographic response to vandetanib was quantified using RECIST (v1.0), biomarker response was measured by comparing posttreatment serum calcitonin and carcinoembryonic antigen (CEA) levels to baseline, and a patient-reported outcome was used to assess clinical benefit. RESULTS Sixteen patients with locally advanced or metastatic MTC received vandetanib for a median (range) 27 (2-52) cycles. Eleven patients remain on protocol therapy. Diarrhea was the primary dose-limiting toxicity. In subjects with M918T RET germline mutations (n = 15) the confirmed objective partial response rate was 47% (exact 95% confidence intervals, 21%-75%). Biomarker partial response was confirmed for calcitonin in 12 subjects and for CEA in 8 subjects. CONCLUSION Using an innovative trial design and selecting patients based on target gene expression, we conclude that vandetanib 100 mg/m(2)/d is a well-tolerated and highly active new treatment for children and adolescents with MEN2B and locally advanced or metastatic MTC. |
| Starting Page | 12035 |
| Ending Page | 12052 |
| Page Count | 18 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/19/15/4239.full.pdf |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/early/2013/06/13/1078-0432.CCR-13-0071.full.pdf |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/early/2013/07/17/1078-0432.CCR-13-0071.full.pdf |
| PubMed reference number | 23766359v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/1078-0432.CCR-13-0071 |
| DOI | 10.1158/1078-0432.ccr-13-0071 |
| Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
| Volume Number | 19 |
| Issue Number | 15 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adolescent (age group) Adrenal Medulla Adverse reaction to drug Biological Markers Calcitonin Confidence Intervals Diarrhea Endocrine Gland Neoplasms Gene Expression Medullary carcinoma of thyroid Multiple Endocrine Neoplasia Type 2a Multiple Endocrine Neoplasia Type 2b Mutation Oncogenes Oral cavity Patients Protein Tyrosine Kinase Proto-Oncogenes Response Evaluation Criteria in Solid Tumors Syndrome Thyroid carcinoma Vandetanib |
| Content Type | Text |
| Resource Type | Article |
