Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00070873" target="_blank" >RIV/65269705:_____/19:00070873 - isvavai.cz</a>

Výsledek na webu

<a href="https://link.springer.com/content/pdf/10.1007%2Fs00280-019-03814-5.pdf" target="_blank" >https://link.springer.com/content/pdf/10.1007%2Fs00280-019-03814-5.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00280-019-03814-5" target="_blank" >10.1007/s00280-019-03814-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial

Popis výsledku v původním jazyce

BackgroundSunitinib is approved for treatment of adults with imatinib-resistant gastrointestinal stromal tumor (GIST) or imatinib intolerance.MethodsThis single-arm, multicenter, multinational phase I/II clinical trial (NCT01396148) enrolled eligible patients aged 6 to &lt;18years with advanced, unresectable GIST with non-mutant KIT, or who demonstrated disease progression or intolerance to imatinib. Patients received sunitinib 15mg/m(2) per day, 4-weeks-on/2-weeks-off (schedule 4/2), for 18 cycles over 24months. Intra-patient dose escalation to 22.5 and subsequently 30mg/m(2) 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.ResultsSix 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 22.5mg/m(2); two of them had a further dose increase to 30mg/m(2). The average daily dose at cycle 3 was 21.1mg/m(2) (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 5.8months (95% CI 2.3not reached). There were no serious adverse events.ConclusionsThe tolerable dose of sunitinib in chemotherapy-naive pediatric patients is at least 20mg/m(2) on schedule 4/2. The safety profile and PK of sunitinib in pediatric patients with GIST are comparable to those in adults.

Název v anglickém jazyce

Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial

Popis výsledku anglicky

BackgroundSunitinib is approved for treatment of adults with imatinib-resistant gastrointestinal stromal tumor (GIST) or imatinib intolerance.MethodsThis single-arm, multicenter, multinational phase I/II clinical trial (NCT01396148) enrolled eligible patients aged 6 to &lt;18years with advanced, unresectable GIST with non-mutant KIT, or who demonstrated disease progression or intolerance to imatinib. Patients received sunitinib 15mg/m(2) per day, 4-weeks-on/2-weeks-off (schedule 4/2), for 18 cycles over 24months. Intra-patient dose escalation to 22.5 and subsequently 30mg/m(2) 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.ResultsSix 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 22.5mg/m(2); two of them had a further dose increase to 30mg/m(2). The average daily dose at cycle 3 was 21.1mg/m(2) (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 5.8months (95% CI 2.3not reached). There were no serious adverse events.ConclusionsThe tolerable dose of sunitinib in chemotherapy-naive pediatric patients is at least 20mg/m(2) on schedule 4/2. The safety profile and PK of sunitinib in pediatric patients with GIST are comparable to those in adults.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer chemotherapy and pharmacology

ISSN

0344-5704

e-ISSN

—

Svazek periodika

84

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

41-50

Kód UT WoS článku

000471238200004

EID výsledku v databázi Scopus

2-s2.0-85064668514