ABSTRACT
Despite treatment with the current standard-of-care therapies, patients with newly diagnosed glioblastoma multiforme (GBM) exhibit dismal prognoses. Bevacizumab has demonstrated activity in patients with recurrent GBM and phase 2 trials indicate that the combination of bevacizumab with standard-of-care therapy is feasible and active for patients with newly diagnosed GBM. Bevacizumab has been granted US approval for use as single-agent therapy for patients with progressive GBM following prior therapy, although it has not received approval for use in patients with GBM in Europe. Phase 3 studies have been initiated in patients with newly diagnosed GBM and are currently recruiting patients. We describe the protocol for the AVAglio phase 3 registration trial, which is designed to evaluate the efficacy and safety of combining bevacizumab with standard-of-care therapy in patients with newly diagnosed GBM.
Subject(s)
Antibodies, Monoclonal , Dacarbazine/analogs & derivatives , Glioblastoma/therapy , Radiotherapy , Adult , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Bevacizumab , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Clinical Protocols , Clinical Trials, Phase III as Topic , Combined Modality Therapy , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Europe , Glioblastoma/diagnosis , Humans , Prognosis , Recurrence , Standard of Care , Temozolomide , Treatment OutcomeABSTRACT
PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma) respond to treatment with procarbazine, lomustine, and vincristine (PCV), with response rates of approximately 80%. However, limited data on second-line treatments are available in patients with recurrent tumors. A novel second-generation alkylating agent, temozolomide, has recently demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme and anaplastic astrocytoma. This study describes the effects of temozolomide in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed AO or AOA who had received previous PCV chemotherapy were treated with temozolomide (150 to 200 mg/m2/d for 5 days per 28-day cycle). The primary end point was objective response. Secondary end points included progression-free survival (PFS), time to progression, overall survival (OS), safety, and tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13 patients (27.1%) experienced a partial response (objective response rate, 43.8%), and 19 patients (39.6%) experienced stable disease. For the entire treatment group, median PFS was 6.7 months and median OS was 10 months. For objective responders, median PFS was 13.1 months and median OS was 16 months. For complete responders, PFS was more than 11. 8 months and OS was more than 26 months. Response correlated with improved survival. Temozolomide was safe and well tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.
