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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.  
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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  
dc.subject.classification
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