-
Something wrong with this record ?
Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial
AC. Verschuur, V. Bajčiová, L. Mascarenhas, R. Khosravan, X. Lin, A. Ingrosso, KA. Janeway,
Language English Country Germany
Document type Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 1997-02-01 to 1 year ago
Medline Complete (EBSCOhost)
from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 1997-02-01 to 1 year ago
Public Health Database (ProQuest)
from 1997-02-01 to 1 year ago
- MeSH
- Antineoplastic Agents administration & dosage adverse effects pharmacokinetics MeSH
- Drug Resistance, Neoplasm MeSH
- Progression-Free Survival MeSH
- Gastrointestinal Neoplasms drug therapy pathology MeSH
- Gastrointestinal Stromal Tumors drug therapy pathology MeSH
- Imatinib Mesylate administration & dosage MeSH
- Humans MeSH
- Adolescent MeSH
- Sunitinib administration & dosage adverse effects pharmacokinetics MeSH
- Treatment Outcome MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase I MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Pediatrics Dana Farber Boston Children's Cancer and Blood Disorders Center Boston MA USA
University Hospital Brno Children's Hospital Brno Czech Republic
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc20006439
- 003
- CZ-PrNML
- 005
- 20200522094549.0
- 007
- ta
- 008
- 200511s2019 gw f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1007/s00280-019-03814-5 $2 doi
- 035 __
- $a (PubMed)31006038
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a gw
- 100 1_
- $a Verschuur, Arnauld C $u Department of Pediatric Hematology and Oncology, Hôpital d'Enfants de la Timone, Assistance Publique-Hôpitaux de Marseille, 13005, Marseille, France. Arnauld.Verschuur@ap-hm.fr.
- 245 10
- $a Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial / $c AC. Verschuur, V. Bajčiová, L. Mascarenhas, R. Khosravan, X. Lin, A. Ingrosso, KA. Janeway,
- 520 9_
- $a 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.
- 650 _2
- $a mladiství $7 D000293
- 650 _2
- $a antitumorózní látky $x aplikace a dávkování $x škodlivé účinky $x farmakokinetika $7 D000970
- 650 _2
- $a vztah mezi dávkou a účinkem léčiva $7 D004305
- 650 _2
- $a chemorezistence $7 D019008
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a gastrointestinální nádory $x farmakoterapie $x patologie $7 D005770
- 650 _2
- $a gastrointestinální stromální tumory $x farmakoterapie $x patologie $7 D046152
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a imatinib mesylát $x aplikace a dávkování $7 D000068877
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a doba přežití bez progrese choroby $7 D000077982
- 650 _2
- $a sunitinib $x aplikace a dávkování $x škodlivé účinky $x farmakokinetika $7 D000077210
- 650 _2
- $a výsledek terapie $7 D016896
- 655 _2
- $a klinické zkoušky, fáze I $7 D017426
- 655 _2
- $a klinické zkoušky, fáze II $7 D017427
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a multicentrická studie $7 D016448
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Bajčiová, Viera $u University Hospital Brno-Children's Hospital, Brno, Czech Republic.
- 700 1_
- $a Mascarenhas, Leo $u Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
- 700 1_
- $a Khosravan, Reza $u Pfizer Inc, San Diego, CA, USA.
- 700 1_
- $a Lin, Xun $u Pfizer Inc, San Diego, CA, USA.
- 700 1_
- $a Ingrosso, Antonella $u Pfizer S.r.L, Milan, Italy.
- 700 1_
- $a Janeway, Katherine A $u Pediatrics, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
- 773 0_
- $w MED00001040 $t Cancer chemotherapy and pharmacology $x 1432-0843 $g Roč. 84, č. 1 (2019), s. 41-50
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/31006038 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20200511 $b ABA008
- 991 __
- $a 20200522094547 $b ABA008
- 999 __
- $a ok $b bmc $g 1525297 $s 1096495
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2019 $b 84 $c 1 $d 41-50 $e 20190420 $i 1432-0843 $m Cancer chemotherapy and pharmacology $n Cancer Chemother Pharmacol $x MED00001040
- LZP __
- $a Pubmed-20200511
