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 |
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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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