BACKGROUND Anaplastic oligodendroglioma (OD) tumors, especially those with the combined loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), are sensitive to chemotherapy. Only limited data are available on the role of chemotherapy in low‐grade OD. The authors retrospectively studied the outcome of the procarbazine, lomustine, and vincristine (PCV) chemotherapy regimen in a group of 16 patients with newly diagnosed OD and 5 patients with recurrent low‐grade OD. METHODS Two groups of patients were studied: newly diagnosed patients with large OD and mixed oligoastrocytomas (OA) and patients with recurrent OD and OA after radiotherapy who still showed nonenhancing tumors. Treatment consisted of standard PCV chemotherapy. In the newly diagnosed and responding patients, radiotherapy was withheld until the time of disease recurrence. Responses were assessed by T2‐weighted magnetic resonance image (MRI) scans. Loss of chromosome 1p and 19q was assessed using fluorescent in situ hybridization with locus‐specific probes. RESULTS Three of five patients with recurrent tumors responded. Thirteen of the 16 newly diagnosed patients showed evidence of response. The median time to disease progression in this group was > 24 months. Only one of these patients experienced disease progression while receiving chemotherapy. Several patients showed a signficant clinical improvement despite only a modest improvement of the tumor on the MRI scans. Even patients without loss of 1p or 19q showed satisfactory responses. No TP53 mutations were found. CONCLUSIONS Newly diagnosed patients with OD tumors, with or without loss of 1p/19q, responded to PCV chemotherapy. Up‐front chemotherapy may be indicated especially for patients with large tumors. MRI scans were of limited value for the assessment of response. A Phase III trial should be initiated to compare radiotherapy with chemotherapy. Cancer 2005. © 2005 American Cancer Society.

The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma. The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the region 1p36. Four of the 24 patients responded (17%). Fifty percent of patients were still free from progression at 6 months and 21% were free from progression at 12 months. Although a clear relation existed between loss of 1p and response to temozolomide chemotherapy, this relation was absent in salvage PCV chemotherapy.

Seven patients are reported with meningitis due to viridans streptococci. These patients represented 5% of culture-proven cases of bacterial meningitis in adults participating in a prospective multicentre clinical trial evaluating the use of dexamethasone. Meningitis was iatrogenic in three patients: one patient had been treated with endoscopic sclerotherapy for oesophageal varices, and two patients had undergone thermocoagulation of the gasserian ganglion for trigeminal neuralgia in the previous days.

INTRODUCTION: Treatment options for recurrent glioblastoma remain limited, with only modest activity of second line chemotherapy. Despite the absence of well controlled trials, bevacizumab is widely used for recurrent glioblastoma. Nonetheless, it remains unclear if the high response rates observed after treatment with bevacizumab translate into an overall survival (OS) benefit. We report the first randomized phase II trial on bevacizumab in recurrent glioblastoma with a control arm without bevacizumab. METHODS: This was multicenter phase II study conducted in 14 Dutch sites. Patients with a first recurrence of a glioblastoma after chemo-irradiation with temozolomide were randomized between treatment with oral lomustine 110 mg/m 2 once every 6 weeks, with bevacizumab 10 mg/kg once every 2 weeks intravenously or with the combination lomustine 110 mg/m 2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Response was assessed using the RANO criteria. Primary endpoint was OS at 9 months. A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination arm. RESULTS: 153 patients were randomized, of which 148 were eligible. After the safety analysis the lomustine dosage in the combination arm was reduced to 90 mg/m 2 because of thrombocytopenia, resulting in bevacizumab dose delays. After reduction the treatment in the combination arm was well tolerated. The percentage 9 month OS (95% confidence interval) was 43% (29, 57) in the lomustine arm, 38% (25, 51) in the bevacizumab arm, and 59% (43, 72) in the bevacizumab/lomustine 90 arm. Response rates were 35-40% for bevacizumab treated patients, and 5% in the lomustine single agent arm. CONCLUSION: This study does not show a meaningful OS at 9 months after treatment with bevacizumab alone. However, the results of combination therapy of bevacizumab with lomustine met the prespecified criterion for further phase III studies. AKNOWLEDGMENTS: This study was supported by an unrestricted grant from Roche Nederland bv.

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