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

Alessandra Fabi, Giulio Metro, Michelangelo Russillo, Antonello Vidiri, Maria Carmine Carapella, Marta Maschio, Francesco Cognetti, Bruno Jandolo, Maria Mirri, Isabella Sperduti, Stefano Telera, Mariantonia Carosi, Andrea Pace

Research output: Contribution to journalArticle

Abstract

Background: In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m2 weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Article number101
JournalBMC Cancer
Volume9
DOIs
Publication statusPublished - Mar 31 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

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