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Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma


Posted on: 06/17/2008

First published on June 16, 2008
Neuro Oncol 2008, DOI:10.1215/15228517-2008-025
© Copyright 2008 by the Society for Neuro-Oncology

Received August 15, 2007
Accepted September 19, 2007

Clinical Investigations

Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma

Nongnuch Sirachainan 1, Samart Pakakasama 1, Anannit Visudtibahn 1, Surang Chiamchanya 1, Lojana Tuntiyatorn 2, Mantana Dhanachai 2, Jiraporn Laothamatas 2, Suradej Hongeng 1*

1 Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
2 Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

 

* To whom correspondence should be addressed. E-mail: rashe@mahidol.ac.th .


   Abstract

The prognosis of children with diffuse intrinsic pontine glioma (DIPG) is very poor. Radiotherapy remains the standard treatment for these patients, but the median survival time is only 9 months. Currently, the use of concurrent radiotherapy with temozolomide (TMZ) has become the standard care for adult patients with malignant gliomas. We therefore investigated this approach in 12 children diagnosed with DIPG. The treatment protocol consisted of concurrent radiotherapy at a dose of 55.8-59.4 Gy at the tumor site with TMZ (75 mg/m2/day) for 6 weeks followed by TMZ (200 mg/m2/day) for 5 days with cis-retinoic acid (100 mg/m2/day) for 21 days with a 28-day cycle after concurrent radiotherapy. Ten of the 12 patients had a clinical response after the completion of concurrent radiotherapy. Seven patients had a partial response, four had stable disease, and one had progressive disease. At the time of the report, 9 of the 12 patients had died of tumor progression, one patient was alive with tumor progression, and two patients were alive with continuous partial response and clinical improvement. The median time to progression was 10.2 ± 3.0 months (95% confidence interval [CI], 4.2-16.1 months). One-year progression-free survival was 41.7% ± 14.2%. The median survival time was 13.5 ± 3.6 months (95% CI, 6.4-20.5 months). One-year overall survival was 58% ± 14.2%. The patients who had a partial response after completion of concurrent radiotherapy had a longer survival time p = 0.036) than did the other patients (those with stable or progressive disease). We conclude that the regimen of concurrent radiotherapy and TMZ should be considered for further investigation in a larger series of patients.

Key Words: children, cis-retinoic acid, concurrent radiotherapy, diffuse intrinsic pontine glioma, temozolomide


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