Phase II trial of irinotecan in children with refractory solid tumors: a Children's Oncology Group Study.
OBJECTIVE
A phase II study was performed to determine the efficacy of irinotecan (IRN) in children with refractory solid tumors. Secondary objectives were to evaluate toxicity, pharmacokinetics, pharmacodynamics, and UGT1A1 genotype.


METHODS
A total of 181 patients were enrolled, of whom 171 were eligible. Patients received IRN 50 mg/m2/d for 5 days repeated every 3 weeks. Pharmacokinetic studies and UGT1A1 genotyping were performed.


RESULTS
Of 161 patients assessable for response, one patient with hepatoblastoma had a complete response, with partial responses observed in patients with medulloblastoma (n = 4), rhabdomyosarcoma (n = 1), neuroblastoma (n = 1), and germinoma (n = 1), for an overall response rate of 5%. Grade 4 neutropenia and grade 3 to 4 diarrhea occurred in less than 7% of the courses administered. Pharmacokinetic studies were available for 79 patients. The mean +/- standard deviation IRN plasma clearance was 374 +/- 148 mL/min/m2, with median relative extent of conversion and relative extent of glucuronidation of 0.05 (range, 0.01 to 0.25) and 2.24 (range, 0.39 to 9.6), respectively. No association between UGT1A1 genotype (n = 61) and toxicity or pharmacokinetic parameters was observed.


CONCLUSIONS
IRN 50 mg/m2/d for 5 days every 21 days is well tolerated, but was not effective as a single agent in a spectrum of solid tumors, with the possible exception of patients with medulloblastoma (16% response rate). There was no association between UGT1A1*28 genotype and toxicity or pharmacokinetic parameters.
Bomgaars
Lisa R
LR
Baylor College of Medicine, Houston, TX, USA. lbomgaars@txccc.org
Bernstein
Mark
M
Krailo
Mark
M
Kadota
Richard
R
Das
Soma
S
Chen
Zhengjia
Z
Adamson
Peter C
PC
Blaney
Susan M
SM
D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D018197:Hepatoblastoma / Q000188:drug therapy; D006801:Humans; D007223:Infant; D000077146:Irinotecan; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme