Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Société Française d'Oncologie Pédiatrique.
ABSTRACT Childhood malignant brain stem tumours have a very poor prognosis with a median survival of 9 months despite radiotherapy. No chemotherapy has improved survival. However, carboplatin has been reported to have activity in glial tumours as well as antitumour synergy with radiation. Our aims were to test the response rate of these tumours to carboplatin alone and to evaluate the efficacy on survival of carboplatin alone followed by concurrent carboplatin and radiotherapy. Patients younger than 16 years with typical clinical and radiological presentation of infiltrating brain stem tumour, as well as histologically-documented cases in the atypical forms, were eligible. Two courses of carboplatin (1050 mg/m2 over 3 days) were administered initially. This treatment was followed by a chemoradiotherapy phase including five weekly carboplatin courses (200 mg/m2) and conventional radiotherapy. 38 eligible patients were included. No tumour response was observed after the initial phase. This schedule of first-line carboplatin followed by concurrent carboplatin and radiotherapy did not improve survival.
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ABSTRACT: Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28d) of temozolomide was studied with the aim of overcoming O(6)-methylguanine methyltransferase (MGMT) mediated resistance. Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75mg/m(2)) after which up to 12 courses of 21d of adjuvant temozolomide (75-100mg/m(2)) were given 4 weekly. The trial used a 2-stage design and passed interim analysis. At diagnosis median age was 8years (2-20years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10-100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9months, 35% (21%, 49%) at 1year and 17% (7%, 30%) at 2years. Median survival was 9.5months (range 7.5-11.4months). There were five 2-year survivors with a median age of 13.6years at diagnosis. This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration.European journal of cancer (Oxford, England: 1990) 09/2013; · 4.12 Impact Factor
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ABSTRACT: The prognosis for children with diffuse intrinsic pontine gliomas (DIPGs) is dismal. Although DIPGs constitute only 10-15 % of all pediatric brain tumors, they are the main cause of death in this group with a median survival of less than 12 months. Standard therapy involves radiotherapy, which produces transient neurologic improvement. Despite several clinical trials having been conducted, including trials on targeted agents to assess their efficacy, there is no clear improvement in prognosis. However, knowledge of DIPG biology is increasing, mainly as a result of research using biopsy and autopsy samples. In this review, we discuss recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy. The discussion also includes novel therapeutic options in DIPG. Continuing multimodal and multitargeted therapies might lead to an improvement in the dismal prognosis of the disease.Paediatric Drugs 05/2013; · 1.88 Impact Factor
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ABSTRACT: BACKGROUND: The prognosis of children with diffuse intrinsic pontine gliomas (DIPG) is dismal. This study aims to evaluate the characteristics and treatment outcome of children with DIPG in a single center. METHODS: We reviewed the outcome of children with DIPG treated at the Oncology Institute of Istanbul University from February 1999 to May 2012. RESULTS: Fifty children (26 female, 24 male) with the median age of 7 years were analyzed. The median duration of symptoms was 30 days. All patients received radiotherapy (RT). Before the year 2000, 12 patients received only RT. Thirty-eight had concomitant and/or adjuvant chemotherapy with RT. Between 2000 and 2004, 17 patients received cis-platinum or vincristine as sensitizers during RT and CCNU + vincristine combination after RT. Since 2004, 21 patients received temozolomide (TMZ) concomitantly during RT and as adjuvant chemotherapy after RT. The median survival time of all patients was 13 months (1-160 months). Patients receiving RT + TMZ had a significantly higher overall survival than patients with only RT (p = 0.018). Patients receiving RT + chemotherapy other than TMZ also had a significantly higher overall survival than patients receiving only RT (p = 0.013). Patients receiving RT + TMZ + and chemotherapy other than TMZ had a significantly higher survival than patients receiving only RT (p = 0.005). CONCLUSION: In our series, patients receiving RT + TMZ and also patients receiving RT + chemotherapy other than TMZ had a significantly higher overall survival than patients treated with only RT. Hence, administering chemotherapy during and after RT seems to prolong survival in some DIPG patients.Child s Nervous System 12/2012; · 1.24 Impact Factor