Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma
Background: Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients.
Methods: We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators’ discretion balanced for tumor entity and canonical prognostic factors served as control.
Results: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724–3.9560, P = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034–10.800, P = .0003) were significantly prolonged compared to the control cohort (n = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n = 11/15, 73%).
Conclusions: This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.
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