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

Abstract

BackgroundTo 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.MethodsSurvival 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.ResultsIn 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.ConclusionIn 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.

A Survival Analysis with Identification of Prognostic Factors in a Series of 110 Patients with Newly Diagnosed Glioblastoma Before and After Introduction of the Stupp Regimen: A Single-Center Observational Study

“…In patients with progression or relapse, who didn't undergo second surgery, salvage chemotherapy and/or symptomatic therapy was considered. Of these cases, 39 patients of Group B received 6-cycles BCNU treatment, according to second-line management scheme, after Temozolomide-based chemotherapy [11], whether those in Group A received only symptomatic drugs, after adjuvant chemo-radiotherapy. group B and in group A.…”

microRNA‑574 inhibits cell proliferation and invasion in glioblastoma multiforme by directly targeting zinc finger E‑box‑binding homeobox 1

“…As the most commonly occurring and malignant type of brain tumour affecting humans, glioma is derived from neural stromal cells and is responsible for 81% of all malignant brain tumours in adults (1,2). Based on the degree of malignancy, gliomas are classified into four histopathologic grades (3).…”

Up‐regulation of miR‐497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl‐2

“…Human gliomas are the most frequent and most aggressive primary brain tumor that exhibits malignant aggressiveness and poor prognosis . Currently, although surgical operation combined with radiotherapy and chemotherapy are effective remedies for the treatment of primary glioma, the prognosis of glioma patients still remains poor, with a median survival time of about 12 months .…”