A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report

Autor: Astrid K. Gnekow, David A. Walker, Daniela Kandels, Susan Picton, null Giorgio Perilongo, Jacques Grill, Tore Stokland, Per Eric Sandstrom, Monika Warmuth-Metz, Torsten Pietsch, Felice Giangaspero, René Schmidt, Andreas Faldum, Denise Kilmartin, Angela De Paoli, Gian Luca De Salvo, Irene Slavc, Giorgio Perilongo, Sue Picton, David Walker, Per Erik Sandstrom, Niels Clausen, Mikko Arola, Olafur Gisli Jonsson, Ofelia Cruz, Aurora Navajas, Anna Teijeiro, Chantal Kalifa, Marie-Anne Raquin, Joris Verlooy, Volkmar Hans, Wolfram Scheurlen, Johannes Hainfellner, James Ironside, Keith Robson, Kari Skullerud, David Scheie, null NN, Marie-Madeleine Ruchoux, Anne Jouvet, Dominique Figarella-Branger, Arielle Lellouch-Toubiana, Daniela Prayer, Milena Calderone, Tim Jaspan, Soren Jacob Bakke, Eli Vazquez, Dominique Couanet, Rolf D. Kortmann, Karin Diekmann, Giovanni Scarzello, Roger Taylor, Knut Lote, Jordi Giralt, Christian Carrie, Jean Louis Habrand, Niels Soerensen, Thomas Czech, Paul Chumas, Bengt Gustavson, Michel Zerah, Bettina Wabbels, Maria Luisa Pinello, Alistair Fielder, Ian Simmons, Terje Christoffersen, Gabriele Calaminus, Knut Brockmann, Ronald Straeter, Friedrich Ebinger, Pablo Hernaiz-Driever, Herwig Lackner, Colin Kennedy, Adam Glaser, Bo Stromberg, Jose Ma Indiano, Chantal Rodary, Eric Bouffet, Didier Frappaz, Angela Emser, Suzanne Stephens, David Machin, Marie-Cécile Le Deley, Thore Egeland, Carolyn Freemann, Martin Schrappe, Richard Sposto
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Cancer Research
Vincristine
Pediatrics
medicine.medical_specialty
Randomised trial
Chemotherapy
Childhood
Low grade glioma
medicine.medical_treatment
law.invention
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
law
Interquartile range
Internal medicine
Glioma
medicine
ddc:610
Etoposide
Cancer och onkologi
business.industry
Pediatrik
medicine.disease
Clinical Trial
Carboplatin
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer and Oncology
chemotherapy
childhood
low grade glioma
randomised trial
antineoplastic combined chemotherapy protocols
brain neoplasms
carboplatin
child
child
preschool
etoposide
female
glioma
humans
induction chemotherapy
infant
male
survival analysis
vincristine
business
030217 neurology & neurosurgery
Progressive disease
medicine.drug
Zdroj: European Journal of Cancer
ISSN: 0959-8049
Popis: Background The use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection. Methods Within the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology–Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m2 × 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02–7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site. Findings No differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively. Interpretation The addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of ‘duration of therapy’ and ‘age at stopping therapy’.
Highlights • A randomised trial in the commonest brain tumour type in children – low grade glioma. • Tumour response assessment at 6 months identifies those at greatest risk of subsequent progression and death. • Intensifying induction treatment with etoposide does not improve progression-free survival. • International consortium successfully recruits from 11 European countries in a childhood brain tumour. • Carboplatin hypersensitivity is reduced by coadministration of etoposide.
Databáze: OpenAIRE
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