Originally published as JCO Early Release 10.1200/JCO.2008.20.8975 on September 21 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Trippett, T. M. Articles by Gore, L. PubMed PubMed Citation Articles by Trippett, T. M. Articles by Gore, L. Social Bookmarking                            What's this?

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

From the Memorial Sloan-Kettering Cancer Center, New York, NY; The University of Texas M. D. Anderson Cancer Center, Houston, TX; Vanderbilt University Medical Center, Nashville, TN; University of Arizona Health Sciences Center, Tucson, AZ; University of Florida, Gainesville, FL; Phoenix Children's Hospital, Phoenix, AZ; Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Children's Healthcare of Atlanta, Atlanta, GA; Bristol-Myers Squibb, Hopewell; Bristol-Myers Squibb, Lawrenceville, NJ; Bristol-Myers Squibb, Wallingford, CT; and the Children's Hospital Center for Cancer and Blood Disorders, Aurora, CO.

Corresponding author: Tanya M. Trippett, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: trippet1{at}mskcc.org.

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/m²) in a 3 + 3 design, plus irinotecan (16 or 20 mg/m²/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/m²/d (pediatric) or 20 mg/m²/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.

Supported by Bristol-Myers Squibb. Editorial assistance for the development of this manuscript was provided by Clinical Insights Inc, with the financial support of Bristol-Myers Squibb and ImClone Systems, Inc.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; and the 13th International Symposium in Pediatric Neuro-Oncology, June 29-July 2, 2008, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?