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’.
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 / Gnekow, A. K.; Walker, D. A.; Kandels, D.; Picton, S.; Perilongo, G.; Grill, J.; Stokland, T.; Sandstrom, P. E.; Warmuth-Metz, M.; Pietsch, T.; Giangaspero, F.; Schmidt, R.; Faldum, A.; Kilmartin, D.; De Paoli, A.; De Salvo, G. L.; Gnekow, A. K.; Slavc, I.; Perilongo, G.; Picton, S.; Walker, D.; Stokland, T.; Sandstrom, P. E.; Clausen, N.; Arola, M.; Jonsson, O. G.; Cruz, O.; Navajas, A.; Teijeiro, A.; Grill, J.; Kalifa, C.; Raquin, M. -A.; Verlooy, J.; Hans, V.; Pietsch, T.; Scheurlen, W.; Hainfellner, J.; Giangaspero, F.; Ironside, J.; Robson, K.; Skullerud, K.; Scheie, D.; Nn, ; Ruchoux, M. -M.; Jouvet, A.; Figarella-Branger, D.; Lellouch-Toubiana, A.; Warmuth-Metz, M.; Prayer, D.; Calderone, M.; Jaspan, T.; Bakke, S. J.; Vazquez, E.; Couanet, D.; Kortmann, R. D.; Diekmann, K.; Scarzello, G.; Taylor, R.; Lote, K.; Giralt, J.; Carrie, C.; Habrand, J. L.; Soerensen, N.; Czech, T.; Chumas, P.; Gustavson, B.; Zerah, M.; Wabbels, B.; Pinello, M. L.; Fielder, A.; Simmons, I.; Christoffersen, T.; Calaminus, G.; Brockmann, K.; Straeter, R.; Ebinger, F.; Hernaiz-Driever, P.; Lackner, H.; Kennedy, C.; Glaser, A.; Stromberg, B.; Indiano, J. M.; Rodary, C.; Bouffet, E.; Frappaz, D.; Faldum, A.; Emser, A.; De Salvo, G. L.; Stephens, S.; Machin, D.; Le Deley, M. -C.; Egeland, T.; Freemann, C.; Schrappe, M.; Sposto, R.. - In: EUROPEAN JOURNAL OF CANCER. - ISSN 0959-8049. - 81:(2017), pp. 206-225. [10.1016/j.ejca.2017.04.019]
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
Perilongo G.;Giangaspero F.;Perilongo G.;Giangaspero F.;Vazquez E.;
2017
Abstract
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’.| File | Dimensione | Formato | |
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Note: https://www.sciencedirect.com/science/article/pii/S0959804917309218
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