Safety and Effectiveness of Bis-Chloroethylnitrosourea Wafer Chemotherapy in Elderly Patients with Recurrent Glioblastoma

Abstract

Objective: To assess the safety and effectiveness of bis-chloroethylnitrosourea (BCNU) wafers in elderly patients with recurrent glioblastoma (GBM). Methods: Patients with recurrent GBM operated on between 2007 and 2014 were divided into 3 groups: >65 years with BCNU wafer implantation, >65 years without BCNU wafer implantation, and ≤65 years with BCNU wafer implantation. We compared survival and complications. Results: A total of 79 patients were identified: 24 in the older BCNU group (median age 68.2 years, 33.3% with a methylated MGMT promoter), 16 in the older non-BCNU group (median age 68.6 years, 31.3% with a methylated MGMT promoter), and 39 in the younger BCNU group (median age 56.8 years). Survival after progression was 9.2 months in the elderly BCNU group and 7.6 months in the elderly non-BCNU group (p = 0.34); overall survival was 17.2 and 15.9 months, respectively (p = 0.35). We found a tendency toward a higher rate of seizures and pneumonia in the older BCNU group. Conclusion: BCNU wafer implantation after resection of recurrent GBM is a reasonably safe treatment in patients aged >65 years. Seizures and systemic infections may occur more frequently, but the trade-off is still favorable as survival may be influenced positively. Higher age should not be regarded as a contraindication for BCNU wafers.

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

“…Acquired resistance to the previous standard of care for GBM, bis-chloroethylnitrosourea (BCNU), leads to an increased sensitivity to TMZ 14 . Because BCNU can still be a component of second-line treatment for GBM 15 – 18 , we tested whether our TMZres cells exhibited altered responsiveness to BCNU. Since the resistant cell lines are populations selected from the wild type cell lines they have a more reproducible phenotype as the variability or heterogeneity of the cell line has decreased.…”

“…For decades BCNU was the standard of care for GBM, and it is still a component of some second-line regimens. Findings from clinical studies examining the efficacy of BCNU in recurrent GBM post-TMZ treatment are inconsistent, with some suggesting BCNU remains active while others demonstrate no benefit 16 – 18 . These TMZres cell line pairs may therefore also prove to be valuable resources for defining contexts in which BCNU is or is not appropriate second-line treatment, and for identifying other, more appropriate therapies for TMZ-resistant GBM.…”

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults

“…There were 8 studies eligible which examined the use of systemic or in situ nitrosureas for the treatment of pGBM eligible and were included in this analysis. Table 2 summarizes the 8 studies [17][18][19][20][21][22][23][24] that examined the use systemic or in situ nitrosoureas for the treatment of pGBM. These studies provided Class III evidence.…”

“…The authors concluded that the regimen was not bene cial. Klein et al [19] retrospectively reviewed a cohort of 79 patients with recurrent GBM and methylated MGMT promoter.…”

Rationale and design of the 500-patient, 3-year, and prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT registry

“…Recently, Klein et al . retrospectively analyzed outcomes in three different group of patients with recurrent GBM [ 46 ]. Median survival after progression was 9.2 months in elderly patients (>65 years) receiving BCNU wafers, 7.6 months in elderly patients not receiving BCNU wafers (p = 0.34), and 9.2 months in younger patients receiving BCNU wafers (p = 0.35).…”