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Chemotherapy with BCNU in recurrent glioma: Analysis of clinical outcome and side effects in chemotherapy-naïve patients

Jungk, Christine ; Chatziaslanidou, Despina ; Ahmadi, Rezvan ; Capper, David ; Bermejo, Justo Lorenzo ; Exner, Janina ; von Deimling, Andreas ; Herold-Mende, Christel ; Unterberg, Andreas

In: BMC Cancer, 16 (2016), Nr. 81. pp. 1-11. ISSN 1471-2407

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Download (835kB) | Lizenz: Creative Commons LizenzvertragChemotherapy with BCNU in recurrent glioma: Analysis of clinical outcome and side effects in chemotherapy-naïve patients by Jungk, Christine ; Chatziaslanidou, Despina ; Ahmadi, Rezvan ; Capper, David ; Bermejo, Justo Lorenzo ; Exner, Janina ; von Deimling, Andreas ; Herold-Mende, Christel ; Unterberg, Andreas underlies the terms of Creative Commons Attribution 3.0 Germany

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Abstract

Background: To date, standardized strategies for the treatment of recurrent glioma are lacking. Chemotherapy with the alkylating agent BCNU (1,3-bis (2-chloroethyl)-1-nitroso-urea) is a therapeutic option even though its efficacy and safety, particularly the risk of pulmonary fibrosis, remains controversial. To address these issues, we performed a retrospective analysis on clinical outcome and side effects of BCNU-based chemotherapy in recurrent glioma. Methods: Survival data of 34 mostly chemotherapy-naïve glioblastoma patients treated with BCNU at 1st relapse were compared to 29 untreated control patients, employing a multiple Cox regression model which considered known prognostic factors including MGMT promoter hypermethylation. Additionally, medical records of 163 patients treated with BCNU for recurrent glioma WHO grade II to IV were retrospectively evaluated for BCNU-related side effects classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 2.0. Results: In recurrent glioblastoma, multiple regression survival analysis revealed a significant benefit of BCNU-based chemotherapy on survival after relapse (p = 0.02; HR = 0.48; 95 % CI = 0.26–0.89) independent of known clinical and molecular prognostic factors. Exploratory analyses suggested that survival benefit was most pronounced in MGMT-hypermethylated, BCNU-treated patients. Moreover, BCNU was well tolerated by 46 % of the 163 patients analyzed for side effects; otherwise, predominantly mild side effects occurred (CTCAE I/II; 45 %). Severe side effects CTCAE III/IV were observed in 9 % of patients including severe hematotoxicity, thromboembolism, intracranial hemorrhage and injection site reaction requiring surgical intervention. One patient presented with a clinically apparent pulmonary fibrosis CTCAE IV requiring temporary mechanical ventilation. Conclusion: In this study, BCNU was rarely associated with severe side effects, particularly pulmonary toxicity, and, in case of recurrent glioblastoma, even conferred a favorable outcome. Therefore BCNU appears to be an appropriate alternative to other nitrosoureas although the efficacy against newer drugs needs further evaluation.

Item Type: Article
Journal or Publication Title: BMC Cancer
Volume: 16
Number: 81
Publisher: BioMed Central; Springer
Place of Publication: London; Berlin; Heidelberg
Date Deposited: 02 Mar 2016 08:36
Date: 2016
ISSN: 1471-2407
Page Range: pp. 1-11
Faculties / Institutes: Medizinische Fakultät Heidelberg > Neurochirurgische Universitätsklinik
Medizinische Fakultät Heidelberg > Institut für Medizinische Biometrie und Informatik
Medizinische Fakultät Heidelberg > Pathologisches Institut
Subjects: 610 Medical sciences Medicine
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