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
Phase 2 or 3 results paper on Carboplatin in Glioma & glioblastoma, in European Journal of Cancer (2017), one of the most cited Europe PMC records with Carboplatin in its title.
Overview
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/m 2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m 2 × 10 wkly) and carboplatin (550 mg/m 2 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'.
Indexed on Europe PMC as PubMed record 28649001 (DOI 10.1016/j.ejca.2017.04.019). Its title names Carboplatin and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, research-article, Randomized Controlled Trial). It was matched automatically to the idea "A skull ultrasound implant that opens the barrier at every cycle" and no figure has been checked by an editor.
One of the most cited trial reports Europe PMC returns for Carboplatin in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Matched by Carboplatin in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.
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