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dc.contributor.author
Fouladi, Maryam
dc.contributor.author
Stewart, Clinton F.
dc.contributor.author
Blaney, Susan M.
dc.contributor.author
Onar Thomas, Arzu
dc.contributor.author
Schaiquevich, Paula Susana
dc.contributor.author
Packer, Roger J.
dc.contributor.author
Gajjar, Amar
dc.contributor.author
Kun, Larry E.
dc.contributor.author
Boyett, James M.
dc.contributor.author
Gilbertson, Richard J.
dc.date.available
2023-03-15T12:37:10Z
dc.date.issued
2010-09
dc.identifier.citation
Fouladi, Maryam; Stewart, Clinton F.; Blaney, Susan M.; Onar Thomas, Arzu; Schaiquevich, Paula Susana; et al.; Phase I trial of lapatinib in children with refractory CNS malignancies: A pediatric brain tumor consortium study; Amer Soc Clinical Oncology; Journal Of Clinical Oncology; 28; 27; 9-2010; 4221-4227
dc.identifier.issn
0732-183X
dc.identifier.uri
http://hdl.handle.net/11336/190576
dc.description.abstract
Purpose: To estimate the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetic properties of lapatinib, a selective epidermal growth factor receptor (EGFR) and ERBB2 inhibitor, in children with refractory or recurrent CNS malignancies. Patients and Methods: Lapatinib was administered orally twice daily at escalating doses starting at 300 mg/m2 to patients who were not (stratum I) or were (stratum II) receiving steroids. Pharmacokinetic studies were performed during the first two courses. Expression of the four ERBB receptors and downstream signaling elements in tumor tissue was evaluated by immunohistochemistry. Results: Fifty-nine patients were enrolled (stratum I, n = 32; stratum II, n = 27). Of 29 patients evaluable for toxicity in stratum I, one experienced a DLT (diarrhea) at 520 mg/m2 twice daily, and all three receiving 1,150 mg/m2 twice daily experienced DLTs (one each of rash, diarrhea, and fatigue). Two of 21 patients evaluable for toxicity in stratum II experienced DLTs of rash at 900 mg/m2 twice daily. Lapatinib dosage was related linearly to area under the [concentration-time] curve from start time to 12 hours later (AUC 0-12) and dose-normalized maximum serum concentration and AUC values for patients in stratum II were both significantly higher (P = .001) than those for patients in stratum I. Frequent, high-level expression of activated (phosphorylated) EGFR and ERBB2 receptors and downstream signal intermediates were observed in tumors, particularly in ependymomas that displayed prolonged stable disease on lapatinib therapy. Conclusion: Lapatinib is well tolerated in children with recurrent CNS malignancies, with rash, diarrhea, and fatigue identified as DLTs. The recommended phase II dose, regardless of steroid use, is 900 mg/m2 twice daily.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Amer Soc Clinical Oncology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
brain tumors
dc.subject
lapatinib
dc.subject.classification
Oncología
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Phase I trial of lapatinib in children with refractory CNS malignancies: A pediatric brain tumor consortium study
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-03-12T15:44:03Z
dc.journal.volume
28
dc.journal.number
27
dc.journal.pagination
4221-4227
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Fouladi, Maryam. No especifíca;
dc.description.fil
Fil: Stewart, Clinton F.. No especifíca;
dc.description.fil
Fil: Blaney, Susan M.. No especifíca;
dc.description.fil
Fil: Onar Thomas, Arzu. No especifíca;
dc.description.fil
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Packer, Roger J.. No especifíca;
dc.description.fil
Fil: Gajjar, Amar. No especifíca;
dc.description.fil
Fil: Kun, Larry E.. No especifíca;
dc.description.fil
Fil: Boyett, James M.. No especifíca;
dc.description.fil
Fil: Gilbertson, Richard J.. No especifíca;
dc.journal.title
Journal Of Clinical Oncology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://ascopubs.org/doi/10.1200/JCO.2010.28.4687
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1200/JCO.2010.28.4687
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