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

Fabi A, Metro G, Russillo M, Vidiri A, Carapella CM, Maschio M, Cognetti F, Jandolo B, Mirri MA, Sperduti I, Telera S, Carosi M, Pace A - BMC Cancer (2009)

Bottom Line: Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed.By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. alessandra.fabi@virgilio.it

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/m(2) 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/m(2) to 100 mg/m(2). 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/m(2) (induction phase) followed by 75-85 mg/m(2) (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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Related in: MedlinePlus

Overall Survival in relation to response to fotemustine (all patients, n = 40). Responders = patients achieving partial response – Non-responders = patients achieving either stable or progressive disease.
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Figure 1: Overall Survival in relation to response to fotemustine (all patients, n = 40). Responders = patients achieving partial response – Non-responders = patients achieving either stable or progressive disease.

Mentions: Median OS was 30 months (95% CI 18.6–42.1). At 24 and 48 months from the start of fotemustine therapy, 87.5% and 57.5% of patients were alive respectively. OS was significantly higher among responders to fotemustine as compared to non-responders (60.8% versus 27.8%, p = 0.007) (figure 1).


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

Fabi A, Metro G, Russillo M, Vidiri A, Carapella CM, Maschio M, Cognetti F, Jandolo B, Mirri MA, Sperduti I, Telera S, Carosi M, Pace A - BMC Cancer (2009)

Overall Survival in relation to response to fotemustine (all patients, n = 40). Responders = patients achieving partial response – Non-responders = patients achieving either stable or progressive disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667532&req=5

Figure 1: Overall Survival in relation to response to fotemustine (all patients, n = 40). Responders = patients achieving partial response – Non-responders = patients achieving either stable or progressive disease.
Mentions: Median OS was 30 months (95% CI 18.6–42.1). At 24 and 48 months from the start of fotemustine therapy, 87.5% and 57.5% of patients were alive respectively. OS was significantly higher among responders to fotemustine as compared to non-responders (60.8% versus 27.8%, p = 0.007) (figure 1).

Bottom Line: Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed.By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. alessandra.fabi@virgilio.it

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/m(2) 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/m(2) to 100 mg/m(2). 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/m(2) (induction phase) followed by 75-85 mg/m(2) (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.

Show MeSH
Related in: MedlinePlus