Nimustine (ACNU) Plus Teniposide (VM26) in Recurrent Glioblastoma

Abstract

Background: In a previous trial (NOA-01), the combination of nimustine and teniposide showed efficacy in previously untreated glioblastoma (GBM). After establishing temozolomide as standard first-line therapy in GBM patients, the nimustine (ACNU)/teniposide (VM-26) combination has been employed as salvage chemotherapy for recurrent GBM. However, data on the toxicity and efficacy of this regimen in recurrent GBM are lacking. Patients and Methods: In two neurooncological centers, all patients with recurrent GBM treated with nimustine (90 mg/m², day 1/42) and teniposide (45–70 mg/m², days 1–3/42) were analyzed retrospectively for progression-free survival (PFS), overall survival (OS) and toxicity. Results: Thirty-five patients (median age 51 years, range 25–71 years) were identified. Six months after chemotherapy initiation, PFS was 29% and the median OS 6 months; 23% of patients were alive ≥1 year after initiation of nimustine-teniposide chemotherapy. Grade 4 hematotoxicity was observed in 12 of 35 patients (34%) and in 14 of 83 evaluable chemotherapy courses (17%). Conclusions: The benefit of the nimustine-teniposide combination is moderate in patients with recurrent GBM. The data support the efficacy of the nimustine-teniposide chemotherapy, but the rate of high-grade hematotoxicity is increased.

Ifosfamide, Carboplatin and Etoposide in Recurrent Malignant Glioma

“…After failure of temozolomide (TMZ), there is no established standard salvage chemotherapy. Nitrosourea compounds such as BCNU, ACNU or CCNU are widely used but have limited efficacy [6 months’ progression-free survival (PFS-6) rates of 19–29%] [2,3,4] and considerable toxicity. Also, salvage therapy with bevacizumab has shown some efficacy in phase II trials [5] but these data have not been sufficient to approve bevacizumab for general use and reimbursement in Europe in this setting.…”

Carmustine (BCNU) plus Teniposide (VM26) in Recurrent Malignant Glioma

“…Although comparisons with other trials and retrospective case series may not be legitimate, this contrasts with the experience with BCNU monotherapy (PFS-6: 17.5%) [15] or procarbacine, BCNU, and vincristine chemotherapy (42%) [17] in chemotherapy-naive GBM patients. More importantly, retrospective series with ACNU/VM26 therapy (PFS-6: 19-29%) [12,13], including heavily pretreated patients, and prospective series with CCNU monotherapy (PFS-6: 13-25%) [11,18], including TMZ-pretreated patients, had a higher PFS-6 than BCNU/VM26 therapy in our retrospective series. To explain the differences between the different series, it has to be taken into account that most patients included in our series received BCNU/VM26 as third- or fourth-line therapy or even later in the course of the disease.…”

“…Also, nitrosoureas such as carmustine (BCNU), lomustine (CCNU), and nimustine (ACNU) have been commonly used for decades in recurrent cases with some efficacy; in a randomized trial using CCNU as the standard arm, a PFS-6 of 19% was found [11]. ACNU alone or in combination with teniposide (VM26) showed a PFS-6 of 19-29% in retrospective case series [12,13]. When ACNU was no longer available in Europe, the Neurooncology Center at the University of Bonn switched from intravenous ACNU to intravenous BCNU application.…”

Prophylactic Use of Pegfilgrastim in Patients Treated with a Nitrosourea and Teniposide for Recurrent Glioma

“…Before chemotherapy, mean leukocyte and thrombocyte counts were similar in the cohorts (leukocyte counts: 6.34 9 10 3 /mm 3 . Leukocyte and thrombocyte counts dropped after chemotherapy in both cohorts, but the relative decrease of leukocyte counts was less pronounced in cohort B compared with cohort A during both periods (p=0.02 and p=0.005, respectively, Figure 2A).…”

“…3,4 Indeed, teniposide and nitrosoureas are two cytostatic drugs that both induce predominantly hematotoxic adverse effects. Teniposide (VM26) is a podophyllotoxin derivate that prevents cell replication by inhibiting the activity of topoisomerase II.…”