Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m2 to 100 mg/m2. Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.Low-dose fotemustine at 65–75 mg/m2 (induction phase) followed by 75–85 mg/m2 (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.Malignant gliomas (MGs) account for approximately 50% of all malignant primary brain tumors in adults [1]. Standard therapy for newly diagnosed disease includes surgical resection when feasible, radiotherapy and chemotherapy. Particularly, the role of chemotherapy has progressively become more important ever since a metanalysis suggested a small but significant increase in the 1-year survival rate of MG patients treated with adjuvant chemotherapy [2]. However, despite optimal treatment, median survival ranges from 12 to 15 months for glioblastoma multiforme (GBM) and from 2 to 5 years for anaplastic gliomas [3]. Such a dismal prognosis is mainly to ascribe to the rapid onset of radio- and/or chemo-resistance as well as to the limited therapeutic options available for MGs recurring after standard treatment.Fotemustine is an alkylating cytotoxic agent belo