Phase II results from a phase I/II study to assess the safety and efficacy of weekly nab-paclitaxel in paediatric patients with recurrent or refractory solid tumours: A collaboration with the European Innovative Therapies for Children with Cancer Network.
Adolescent
Age Factors
Albumins
/ administration & dosage
Antineoplastic Agents, Phytogenic
/ administration & dosage
Bone Neoplasms
/ drug therapy
Child
Child, Preschool
Drug Administration Schedule
Europe
Female
Humans
Infant
Male
Neuroblastoma
/ drug therapy
Paclitaxel
/ administration & dosage
Progression-Free Survival
Rhabdomyosarcoma
/ drug therapy
Sarcoma, Ewing
/ drug therapy
Time Factors
Tissue Distribution
Young Adult
Albumin-bound paclitaxel
Ewing sarcoma
Neuroblastoma
Paediatric
Rhabdomyosarcoma
Solid tumour
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
13
12
2019
revised:
01
04
2020
accepted:
23
04
2020
pubmed:
20
6
2020
medline:
31
12
2020
entrez:
20
6
2020
Statut:
ppublish
Résumé
The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study. Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive. In this phase II study, limited activity was observed; however, the safety of nab-paclitaxel in paediatric patients was confirmed. NCT01962103 and EudraCT 2013-000144-26.
Sections du résumé
BACKGROUND
The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study.
PATIENTS AND METHODS
Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m
RESULTS
Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive.
CONCLUSIONS
In this phase II study, limited activity was observed; however, the safety of nab-paclitaxel in paediatric patients was confirmed.
TRIAL REGISTRATION
NCT01962103 and EudraCT 2013-000144-26.
Identifiants
pubmed: 32554315
pii: S0959-8049(20)30234-3
doi: 10.1016/j.ejca.2020.04.031
pii:
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
Antineoplastic Agents, Phytogenic
0
Paclitaxel
P88XT4IS4D
Banques de données
ClinicalTrials.gov
['NCT01962103']
EudraCT
['2013-000144-26']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-97Informations de copyright
Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Conflict of interest statement G.B. reports serving in a consulting or advisory role for Clinigen Group and receiving travel expenses from Jazz Pharmaceuticals. J.C.C. reports serving in a consulting or advisory role for Bayer and Roche. F.D. reports serving in a consulting or advisory role for Bristol-Myers Squibb and Celgene (a Bristol-Myers Squibb Company), from which his institution has received funds, and receiving travel expenses from Bristol-Myers Squibb. L.M. reports serving in a consulting or advisory role for Novartis, AstraZeneca, Roche Genentech, Bayer, Amgen and MundiPharma; receiving honoraria for educational events from Celgene (a Bristol-Myers Squibb Company) and Novartis and receiving travel expenses from MundiPharma, Celgene (a Bristol-Myers Squibb Company) and Amgen. S.G.M. reports being in a paid advisory role for Loxo Oncology and Clinigen Group for work performed outside of the current study. R.S. reports serving as an employee of and holding stock/ownership in Bristol-Myers Squibb. N.C. reports serving as an employee of and holding stock/ownership in Bristol-Myers Squibb. Y.l.-B. reports serving as an employee of Celgene (a Bristol-Myers Squibb Company) International A Bristol-Myers Squibb Company and holding stock/ownership in Bristol-Myers Squibb. M.S. reports serving as an employee of Celgene (a Bristol-Myers Squibb Company) International A Bristol-Myers Squibb Company and holding stock/ownership in Bristol-Myers Squibb. G.V. reports receiving travel expenses from Bristol-Myers Squibb. All other authors declare no conflict of interest