Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: A study of the Pediatric Oncology Experimental Therapeutic Investigators' Consortium Journal Article


Authors: Trippett, T. M.; Herzog, C.; Whitlock, J. A.; Wolff, J.; Kuttesch, J.; Bagatell, R.; Hunger, S. P.; Boklan, J.; Smith, A. A.; Arceci, R. J.; Katzenstein, H. M.; Harbison, C.; Zhou, X. F.; Lu, H. L.; Langer, C.; Weber, M.; Gore, L.
Article Title: Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: A study of the Pediatric Oncology Experimental Therapeutic Investigators' Consortium
Abstract: Purpose To determine the dose of cetuximab that can be safely combined with irinotecan for treatment of pediatric and adolescent patients with refractory solid tumors. Patients and Methods This open-label, phase I study enrolled patients ages 1 to 18 years with advanced refractory solid tumors, including tumors of the CNS. Patient cohorts by age group (children, ages 1 to 12 years; adolescents, ages 13 to 18 years) received escalating weekly doses of cetuximab (75, 150, 250 mg/m(2)) in a 3 + 3 design, plus irinotecan (16 or 20 mg/m(2)/d) for 5 days for 2 consecutive weeks every 21 days. The primary end points were establishing the maximum-tolerated dose (MTD), recommended phase II dose (RPIID), and pharmacokinetics of the combination. Preliminary safety and efficacy data were also collected. Results Twenty-seven children and 19 adolescents received a median of 7.1 and 6.0 weeks of cetuximab therapy, respectively. Cetuximab 250 mg/m2 weekly plus irinotecan 16 mg/m(2)/d (pediatric) or 20 mg/m(2)/d (adolescent) have been established as the MTD/RPIID. Dose-limiting toxicities included diarrhea and neutropenia. Mild to moderate (grade 1 to 2) acneiform rash occurred in a majority of patients; no grade 3 to 4 rashes were observed. Cetuximab demonstrated dose-dependent clearance in both children and adolescents, similar to that in adults. There were two confirmed partial responses, both in patients with CNS tumors. Stable disease was achieved in 18 patients overall, including 10 patients with CNS tumors (38.5%). Conclusion The cetuximab/irinotecan combination can be given safely to children and adolescents with cancer. Promising activity, particularly in CNS tumors, warrants phase II evaluation of this regimen.
Keywords: gene amplification; carcinoma; neck; expression; squamous-cell; malignant glioma; metastatic colorectal-cancer; combination; growth-factor-receptor; head; plus cetuximab
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 30
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-10-01
Start Page: 5102
End Page: 5108
Language: English
ACCESSION: ISI:000270875100029
DOI: 10.1200/jco.2008.20.8975
PROVIDER: wos
PUBMED: 19770383
PMCID: PMC5321093
Notes: --- - Article - "Source: Wos"
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  1. Tanya M Trippett
    120 Trippett