Abstract | BACKGROUND: The objectives of this phase I study were to determine the maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics of a 24-hour continuous intravenous infusion of trabectedin administered to children and adolescents with refractory or relapsed solid tumors. PROCEDURE: Patients between the ages of 4 and 16 years old with refractory solid tumors received trabectedin as a 24-hour infusion every 21 days. Dexamethasone and prophylactic growth factor support were administered with each cycle. Pharmacokinetic studies were conducted during cycle 1. RESULTS: Patients (n = 12) median (range) age 14.5 (8-16) years received trabectedin at 1.1 (n = 3), 1.5 (n = 6), or 1.7 (n = 3) mg/m(2). At the 1.5 mg/m(2) dose level, one patient had dose limiting anorexia and fatigue. At 1.7 mg/m(2), two patients experienced dose limiting toxicity, dehydration, and gamma-glutamyl transpeptidase elevation. Non-dose limiting toxicities included elevated serum transaminases, myelosuppression, nausea, emesis, and fatigue. Plasma pharmacokinetic parameters were similar to historical data in adults. One partial response was observed in a patient with neuroendocrine carcinoma. Stable disease (≥6 cycles) was achieved in three patients ( osteosarcoma n = 2, desmoplastic small round cell tumor n = 1). CONCLUSIONS: The MTD of trabectedin in pediatric patients with refractory solid tumors is 1.5 mg/m(2) IV over 24 hours every 21 days. Dexamethasone to ameliorate hepatic toxicity and prophylactic growth factor support are required.
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Authors | Meredith K Chuk, Alberta Aikin, Trish Whitcomb, Brigitte C Widemann, Peter Zannikos, Eliel Bayever, Frank M Balis, Elizabeth Fox |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 59
Issue 5
Pg. 865-9
(Nov 2012)
ISSN: 1545-5017 [Electronic] United States |
PMID | 22847981
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Intramural)
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Copyright | Copyright © 2012 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents, Alkylating
- Antineoplastic Agents, Hormonal
- Dioxoles
- Tetrahydroisoquinolines
- Dexamethasone
- Trabectedin
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Topics |
- Adolescent
- Antineoplastic Agents, Alkylating
(administration & dosage, adverse effects, pharmacokinetics)
- Antineoplastic Agents, Hormonal
(administration & dosage, adverse effects)
- Child
- Dexamethasone
(administration & dosage, adverse effects)
- Dioxoles
(administration & dosage, adverse effects, pharmacokinetics)
- Female
- Humans
- Male
- Neoplasm Recurrence, Local
(drug therapy)
- Neoplasms
(drug therapy)
- Recurrence
- Tetrahydroisoquinolines
(administration & dosage, adverse effects, pharmacokinetics)
- Time Factors
- Trabectedin
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