Phase I dose-escalation study of volasertib in pediatric patients with acute leukemia or advanced solid tumors.
Pediatr Blood Cancer
; 66(10): e27900, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31276318
ABSTRACT
BACKGROUND:
Volasertib induces mitotic arrest and apoptosis by targeting Polo-like kinases. In this phase I dose-escalation study, the maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of volasertib were determined in pediatric patients.METHODS:
Patients aged 2 to <18 years with relapsed/refractory acute leukemia/advanced solid tumors (ST) without available effective treatments were enrolled-cohort C1 (aged 2 to <12 years); cohort C2 (aged 12 to <18 years). The patients received volasertib intravenously (starting dose 200 mg/m2 body surface area on day 1, every 14 days). The primary endpoint was the pediatric MTD for further development.RESULTS:
Twenty-two patients received treatment (C1 leukemia, n = 4; ST, n = 8; C2 leukemia, n = 3; ST, n = 7). No dose-limiting toxicities (DLTs) occurred up to 300 mg/m2 volasertib in C1; two patients in C2, at 250 mg/m2 volasertib, had DLTs in cycle 1, one of which led to death; therefore, the MTD of volasertib in C2 was 200 mg/m2 . The most common grade 3/4 adverse events (all patients) were febrile neutropenia, thrombocytopenia, and neutropenia (41% each). Stable disease (SD) was the best objective response (leukemia, n = 5; ST, n = 2); the duration of SD was short in all patients, except in one with an ST. PK profiles were generally comparable across dose groups and were consistent with those in adults.CONCLUSION:
The pediatric MTD/dose for further development was identified. There were no unexpected safety or PK findings; limited antitumor/antileukemic activity was demonstrated.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pteridinas
/
Leucemia
/
Neoplasias
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adolescent
/
Child
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Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pediatr Blood Cancer
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia