Article

High-grade glioma in children under 5 years of age: A chemotherapy only approach with the BBSFOP protocol

Department of Pediatric and Adolescent, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejuif cedex, France. <>
European Journal of Cancer (Impact Factor: 4.82). 12/2006; 42(17):2939-45. DOI: 10.1016/j.ejca.2006.06.021
Source: PubMed

ABSTRACT The aim of this study was to evaluate a chemotherapy strategy that avoids radiotherapy in first-line treatment of young children with high-grade glioma. A total of 21 children under 5 years of age received the BBSFOP protocol, comprising seven cycles of three drug pairs (carboplatin/procarbazine, cisplatin/etoposide and vincristine/cyclophosphamide) administered over a 16 month period. Radiotherapy was performed in case of recurrence/progression. Median age at diagnosis was 23 months. Histology was classified as World Health Organisation (WHO) grade III in 13 and grade IV in 8. Of the 13 children with a residual tumour, chemotherapy induced 2 partial responses (PR), 1 minor response (MR) and 1 stable disease (SD) with no recurrent disease. Five-year progression-free survival was 35% and 5-year overall survival was 59%, with a median follow-up of 5.2 years. At the last update, 12 children were alive (10 without radiotherapy). In conclusion, this study shows that an adjuvant chemotherapy first approach is safe and allows radiotherapy to be avoided in selected children.

0 Followers
 · 
95 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High-grade gliomas represent a formidable challenge to paediatric oncologists. The second most common malignant brain tumour of childhood, little progress has been made in the outcome of these tumours in the last four decades. Outcome remains dire with less than 20 % of patients surviving. Current treatment consists of maximal resection and radiotherapy, with chemotherapy both in conjunction with and adjuvant to radiotherapy being added more recently. Yet much of the evidence for the use of chemotherapy is extrapolated from adult data, and evidence for its use in the paediatric population is weak. Recent advances in the biology of high-grade glioma in children identify epigenomic subgroups distinct from those seen in adults, suggesting a separate tumourigenic mechanism and delineating a separate disease entity. The time may be to move forward with a different way of thinking about paediatric tumours. With biological insight comes the promise of more effective therapies, rationally targeted towards the biology of the tumour. This review addresses the current advances in paediatric high-grade glioma and how we can move forward to translate this into improved outcomes for these patients.
    Current Oncology Reports 12/2014; 16(12):414. DOI:10.1007/s11912-014-0414-0 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric brain tumors are most common cancers in childhood and among the leading causes of death in children. Chemotherapy has been used as adjuvant (i.e. after) or neoadjuvant (i.e. before) therapy to surgery and radiotherapy for the management of pediatric brain tumors for more than four decades and gained more attention in the recent two decades. Although chemotherapy has demonstrated its effectiveness in the management of some pediatric brain tumors, failure or inactiveness of chemotherapy is commonly met in the clinics and clinical trials. Some of these failures might be attributed to the blood-brain barrier (BBB), limiting the penetration of systemically administered chemotherapeutics into pediatric brain tumors. Therefore, various strategies have been developed and used to address this issue. Herein, we review different methods reported in the literature to circumvent the BBB for enhancing the present of chemotherapeutics in the brain to treat pediatric brain tumors.
    Pharmaceutical Research 08/2013; DOI:10.1007/s11095-013-1196-z · 3.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OPINION STATEMENT: Gliomas are the most common brain tumor in children and represent nearly 50 % of all pediatric central nervous system (CNS) tumors. They are a heterogeneous group of diseases, ranging from highly malignant and frequently fatal to histologically benign and curable by surgery alone. A uniform treatment approach to these tumors is not practical, due to their histological and biological heterogeneity. Low-grade gliomas (LGGs) are best treated with maximally safe surgical resection, generally achievable for hemispheric or cerebellar locations. Patients with deep midline, optic pathway/hypothalamic, and brain stem locations should undergo subtotal resection or biopsy only. If a complete resection is not feasible, subtotal resection followed by adjuvant chemotherapy or radiotherapy is the standard approach; however, observation alone with serial neuroimaging is used in some asymptomatic, surgically inaccessible lesions. Chemotherapy is used first-line in cases of residual or progressive disease, to avoid or delay radiation therapy and its associated side effects. Regimens demonstrating objective responses and increased progression free survival (PFS) include carboplatin and vincristine (CV), thioguanine/procarbazine/CCNU/vincristine (TPCV), or weekly vinblastine. High-grade gliomas (HGGs) are less common in children than in adults, though are similar in their aggressive clinical behavior, resistance to therapy, and dismal outcomes. There is not a single "standard of care" therapy for non-metastatic HGGs, but generally accepted is an aggressive attempt at a complete surgical resection, followed by multimodality therapy with focal radiation and chemotherapy. The use of temozolomide (TMZ) during and following radiotherapy is common, though it appeared not to improve the outcome in a cooperative group clinical trial when compared to an historical control cohort. The angiogenesis inhibitor bevacizumab, used alone or in combination with irinotecan, is also commonly used as maintenance therapy after radiation. Current trials are prospectively comparing TMZ to newer agents (vorinostat, bevacizumab) in a randomized phase II trial. Brainstem gliomas are a unique category of childhood gliomas. Approximately 80 % of childhood brainstem gliomas arise within the pons as diffuse intrinsic pontine gliomas (DIPG). When biopsied, these are usually HGGs and carry a dismal prognosis. Standard therapy is focal radiation (54-58 Gy), preferably on a clinical trial testing concurrent chemotherapy or biologic agent. No standard chemotherapy agent has impacted survival. The remaining 20 % of brainstem gliomas are low-grade, arise in the midbrain, dorsal medulla, or cervicomedullary junction, and are indolent in nature with a much better prognosis. Improvement in the outcome of all childhood gliomas will require increased knowledge of the underlying biology of these tumors, in order to treat with more biologically based and precise therapies.
    Current Treatment Options in Neurology 02/2013; 15(3). DOI:10.1007/s11940-013-0225-x · 2.18 Impact Factor

Full-text (2 Sources)

Download
33 Downloads
Available from
May 22, 2014