|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 23, No 25 (September 1), 2005: pp. 6172-6180 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.11.429 Phase I and Pharmacokinetic Study of Gefitinib in Children With Refractory Solid Tumors: A Children’s Oncology Group StudyFrom the Departments of Hematology-Oncology and Pharmaceutical Sciences, St Jude Children’s Research Hospital; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN; Keck School of Medicine, University of Southern California, Los Angeles, CA; Sainte-Justine Hospital, Montreal, Quebec, Canada; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; Texas Children’s Cancer Center/Baylor College of Medicine, Houston, TX; James Whitcomb Riley Hospital for Children, Indianapolis, IN; Children’s National Medical Center-D.C., Washington, DC; and Children’s Hospital of Philadelphia, Philadelphia, PA Address reprint requests to Najat C. Daw, MD, Department of Hematology-Oncology, Mail Stop 260, St Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105-2794; e-mail: najat.daw{at}stjude.org PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28).
RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non–dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing’s sarcoma had a partial response. Disease stabilized for 8 to CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued. Supported by grant No. CA 97452 from the National Cancer Institute, Bethesda, MD, and by AstraZeneca, Wilmington, DE. Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA. Authors’ disclosures of potential conflicts of interest are found at the end of this article.
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
60 weeks in two patients with Wilms’ tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 µg/mL (range, 1.2 to 3.6 µg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. 
