A phase I trial and pharmacokinetic study of a 24-hour infusion of trabectedin in children and adolescents with relapsed or refractory solid tumors
Pediatric Blood & Cancer, 08/20/2012
Chuk MK et al. – The maximum tolerated dose (MTD) of trabectedin in pediatric patients with refractory solid tumors is 1.5mg/m2 IV over 24hours every 21 days. Dexamethasone to ameliorate hepatic toxicity and prophylactic growth factor support are required.Methods
- 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.
- 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/m2.
- At the 1.5mg/m2 dose level, one patient had dose limiting anorexia and fatigue.
- At 1.7mg/m2, 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).