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

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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

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fotemustine
Methyltransferases
Glioma
Methylation
DNA
Therapeutics
Appointments and Schedules

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Treatment of recurrent malignant gliomas with fotemustine monotherapy : Impact of dose and correlation with MGMT promoter methylation. / Fabi, Alessandra; Metro, Giulio; Russillo, Michelangelo; Vidiri, Antonello; Carapella, Maria Carmine; Maschio, Marta; Cognetti, Francesco; Jandolo, Bruno; Mirri, Maria; Sperduti, Isabella; Telera, Stefano; Carosi, Mariantonia; Pace, Andrea.

In: BMC Cancer, Vol. 9, 101, 31.03.2009.

Research output: Contribution to journalArticle

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title = "Treatment of recurrent malignant gliomas with fotemustine monotherapy: Impact of dose and correlation with MGMT promoter methylation",
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.",
author = "Alessandra Fabi and Giulio Metro and Michelangelo Russillo and Antonello Vidiri and Carapella, {Maria Carmine} and Marta Maschio and Francesco Cognetti and Bruno Jandolo and Maria Mirri and Isabella Sperduti and Stefano Telera and Mariantonia Carosi and Andrea Pace",
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T1 - Treatment of recurrent malignant gliomas with fotemustine monotherapy

T2 - Impact of dose and correlation with MGMT promoter methylation

AU - Fabi, Alessandra

AU - Metro, Giulio

AU - Russillo, Michelangelo

AU - Vidiri, Antonello

AU - Carapella, Maria Carmine

AU - Maschio, Marta

AU - Cognetti, Francesco

AU - Jandolo, Bruno

AU - Mirri, Maria

AU - Sperduti, Isabella

AU - Telera, Stefano

AU - Carosi, Mariantonia

AU - Pace, Andrea

PY - 2009/3/31

Y1 - 2009/3/31

N2 - 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.

AB - 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.

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