A Phase II trial of paclitaxel and topotecan with filgrastim in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma

Purpose: Therapy for high-grade gliomas remains unsatisfactory. Paclitaxel and topotecan have separately demonstrated activity against gliomas. We conducted a Phase II trial of these agents in combination with filgrastim (G-CSF) in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.Patients and Methods: Adult patients with radiographic evidence of recurrent or progressive tumor following primary therapy were eligible for study. Patients received paclitaxel 175 mg/m² IV over 3 h on day 1 and topotecan 1.0 mg/m ² IV over 30 min on days 1–5. Filgrastim 5 g/kg was given days 6–14 for neutrophil support. Treatment cycles were repeated every 21 days.Results: Twenty patients were enrolled on study, and seventeen were considered evaluable for response. Two patients (12/%) exhibited partial remission and seven patients (41/%) exhibited stable disease in response to therapy. Hematologic toxicity was common with 25 /% of patients experiencing grade III or IV leukopenia despite G-CSF support. Two patients died of infectious complications on protocol, prompting suspension of further accrual.Conclusion: Paclitaxel and topotecan with G-CSF support exhibits modest activity in adults with recurrent or refractory glioblastoma and anaplastic astrocytoma. The significant hematotoxicity encountered, however, cannot justify further investigation of this combination in patients with high grade brain tumors.Supported with grant funding from: GlaxoSmithKline Pharmaceuticals Collegeville, PA