Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial.
Cancer Chemother Pharmacol
; 84(1): 41-50, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-31006038
ABSTRACT
BACKGROUND:
Sunitinib is approved for treatment of adults with imatinib-resistant gastrointestinal stromal tumor (GIST) or imatinib intolerance.METHODS:
This single-arm, multicenter, multinational phase I/II clinical trial (NCT01396148) enrolled eligible patients aged 6 to < 18 years with advanced, unresectable GIST with non-mutant KIT, or who demonstrated disease progression or intolerance to imatinib. Patients received sunitinib 15 mg/m2 per day, 4-weeks-on/2-weeks-off (schedule 4/2), for ≤ 18 cycles over 24 months. Intra-patient dose escalation to 22.5 and subsequently 30 mg/m2 were permitted based on individual patient tolerability and supported by real-time pharmacokinetics (PK). Primary objective was PK characterization. Secondary objectives included safety, antitumor activity and PK/pharmacodynamic relationships.RESULTS:
Six patients were enrolled with median (range) age of 14 (13-16) years. All six patients completed at least three treatment cycles, with one completing all 18 cycles. Five patients had a dose increase to 22.5 mg/m2; two of them had a further dose increase to 30 mg/m2. The average daily dose at cycle 3 was 21.1 mg/m2 (n = 6). Steady-state plasma concentrations were reached by day 15, cycle 1. No tumor responses were observed, but three patients had stabilization of the disease (50%). Median progression-free survival was 5.8 months (95% CI 2.3-not reached). There were no serious adverse events.CONCLUSIONS:
The tolerable dose of sunitinib in chemotherapy-naïve pediatric patients is at least 20 mg/m2 on schedule 4/2. The safety profile and PK of sunitinib in pediatric patients with GIST are comparable to those in adults.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tumores del Estroma Gastrointestinal
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Sunitinib
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Neoplasias Gastrointestinales
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Antineoplásicos
Tipo de estudio:
Clinical_trials
Límite:
Adolescent
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Female
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Humans
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Male
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia