In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 17, No. 6 ( 1999-06), p. 1815-1815
Abstract:
PURPOSE: In a preclinical model of neuroblastoma, administration of irinotecan daily 5 days per week for 2 consecutive weeks ([qd × 5] × 2) resulted in greater antitumor activity than did a single 5-day course with the same total dose. We evaluated this protracted schedule in children. PATIENTS AND METHODS: Twenty-three children with refractory solid tumors were enrolled onto a phase I study. Cohorts received irinotecan by 1-hour intravenous infusion at 20, 24, or 29 mg/m 2 (qd × 5) × 2 every 21 days. RESULTS: The 23 children (median age, 14.1 years; median prior regimens, two) received 84 courses. Predominant diagnoses were neuroblastoma (n = 5), osteosarcoma (n = 5), and rhabdomyosarcoma (n = 4). The dose-limiting toxicity was grade 3/4 diarrhea and/or abdominal cramps in six of 12 patients treated at 24 mg/m 2 , despite aggressive use of loperamide. The maximum-tolerated dose (MTD) on this schedule was 20 mg/m 2 /d. Five patients had partial responses and 16 had disease stabilization. On day 1, the median systemic exposure to SN-38 (the active metabolite of irinotecan) at the MTD was 106 ng-h/mL (range, 41 to 421 ng-h/mL). CONCLUSION: This protracted schedule is well tolerated in children. The absence of significant myelosuppression and encouraging clinical responses suggest compellingly that irinotecan be further evaluated in children using the (qd × 5) × 2 schedule, beginning at a dose of 20 mg/m 2 . These results imply that data obtained from xenograft models can be effectively integrated into the design of clinical trials.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.1999.17.6.1815
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
1999
detail.hit.zdb_id:
2005181-5