Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
Grantová podpora
15958
Cancer Research UK - United Kingdom
CRUK/02/014
Cancer Research UK - United Kingdom
PubMed
26271204
DOI
10.1016/j.ejca.2015.06.123
PII: S0959-8049(15)00649-8
Knihovny.cz E-zdroje
- Klíčová slova
- Alkylating agent, CYP2B6, CYP3A4, Constitutive androstane receptor, Efficacy, Ewing sarcomas, Gender, Interaction, Metabolism, Toxicity,
- MeSH
- antitumorózní látky alkylující aplikace a dávkování škodlivé účinky MeSH
- časové faktory MeSH
- cyklofosfamid aplikace a dávkování MeSH
- disparity zdravotního stavu MeSH
- doxorubicin aplikace a dávkování MeSH
- Ewingův sarkom farmakoterapie patologie MeSH
- ifosfamid aplikace a dávkování MeSH
- lidé MeSH
- mladiství MeSH
- nádory kostí farmakoterapie patologie MeSH
- náhrada léků MeSH
- přežití po terapii bez příznaků nemoci MeSH
- progrese nemoci MeSH
- proporcionální rizikové modely MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování škodlivé účinky MeSH
- rizikové faktory MeSH
- sexuální faktory MeSH
- vinkristin aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- antitumorózní látky alkylující MeSH
- cyklofosfamid MeSH
- doxorubicin MeSH
- ifosfamid MeSH
- vinkristin MeSH
BACKGROUND: Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. PATIENTS AND METHODS: Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. RESULTS: EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). CONCLUSION: Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. TRIAL NUMBERS: NCT00987636 and EudraCT 2008-003658-13.
Cancer Research UK Cancer Trials Unit University of Birmingham Birmingham
Cliniques Universitaires Saint Luc Brussels Belgium
Department of Paediatric Hematology and Oncology University Hospital Muenster Germany
Emma Children's Hospital Academic Medical Center Amsterdam The Netherlands
Institut d'Hématologie et d'Oncologie Pédiatrie Lyon France
Institute Gustave Roussy Villejuif France
Institute Gustave Roussy Villejuif France; Paris Sud University Le Kremlin Bicêtre France
Leiden University Medical Center Leiden The Netherlands
Royal Manchester Children's Hospital Manchester United Kingdom
Skåne University Hospital Lund University Lund Sweden
St Anna Children's Hospital and Research Institute Vienna Austria
The Royal Marsden NHS Foundation Trust London United Kingdom
United Kingdom Sir James Spence Institute Newcastle upon Tyne United Kingdom
University Children's Hospital Basel Basel Switzerland
University College Hospital London United Kingdom
Vestische Kinder und Jugendklinik Datteln Witten Herdecke University Datteln Germany
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