Treatment of gliomatosis cerebri with temozolomide: A retrospective study of the AINO (Italian Association for Neuro- Oncology)

Abstract

2033 Background: The optimal management for patients with primary gliomatosis cerebri is unknown, and some recent studies suggest that temozolomide could be useful as an upfront treatment. Methods: Between 1999 and 2005, 46 patients with biopsy proven gliomatosis cerebri were treated with temozolomide either upfront or at progression after prior radiotherapy/chemotherapy. Histological diagnoses were as follows: glioblastoma in 3 patients, malignant glioma in 8, anaplastic astrocytoma in 8, gemistocytic astrocytoma in 2, astrocytoma in 13, anaplastic oligodendroglioma in 1, anaplastic oligoastrocytoma in 1, oligoastrocytoma in 1, oligodendroglioma in 4, glial proliferation consistent with GC in 5. Median age was 49 years (range 14–70), with 20 males and 26 females and a median KPS at diagnosis of 80 (range 50–90). Twenty-three out of 46 (50%) pre-treatment MRI demonstrated some degree of contrast enhancement. Twenty-three of 46 patients were treated upfront, while 23 had received prior radiation therapy or nitrosourea-based chemotherapy. All patients received temozolomide 200 mg/m2 die for 5 days every 4 weeks until progression or unacceptable toxicity. Response was evaluated, according to Macdonald criteria, on T1-weighted with Gadolinium and FLAIR images. Results: Two patients (4%) showed a CR of the contrast enhancing area, 2 patients (4%) a PR, 5 (11%) a minor response, 18 (39%) a SD and 19 (42%) a PD. Overall response rate (CR + PR + “minor response”) was 19%, while a clinical benefit was observed in 13/46 patients (28%). Median TTP was 9 months (range 1–27), and median survival 14 months (range 3–123). PFS at 6 months was 57%, at 12 months 35%. Oligodendroglial tumours showed a 38% response rate and a TTP of 11 months. Response rate was higher among patients treated at progression compared to those treated upfront (13% versus 26%). Grade III-IV haematological toxicity was mild. Conclusions: Temozolomide has some activity in primary GC (19% response rate), and is well tolerated. A significant neurological improvement can be observed in patients with either response or stable disease on MRI. To improve the efficacy of temozolomide in the upfront setting (in order to delay a large field RT), a phase II study with a dose-dense regimen is ongoing. No significant financial relationships to disclose.