title: Low-dose fotemustine for recurrent malignant glioma: a multicenter phase II study.
abstract: Fotemustine at the conventional dose of 100 mg/m(2) is an active treatment for recurrent malignant gliomas (RMGs). However, it is associated with a relevant incidence of severe myelotoxicity, which is not justified in the palliative setting of this disease. This study was conducted to address whether administration of fotemustine at 60 mg/m(2) (induction) followed by 75 mg/m(2) (maintenance) would preserve clinical activity with the advantage of improved tolerance. Forty patients with RMGs pretreated with ≤2 lines of chemotherapy were enrolled. Median age was 57 years (26-80) and median Karnofsky performance status was 80 (60-100). Thirty-one patients (77.5%) had tissue available for analysis of the O(6)-methylguanine methyltransferase (MGMT) gene promoter which was found to be methylated in 14 cases (45%). Overall, 8 partial responses (20%) and 13 disease stabilizations (32.5%) were observed for a disease-control rate of 52.5%. At 6 months, 21% of patients were free from progression. Grades 3 and 4 platelet and white blood cell toxicity occurred in ≤10% of patients, and no patients discontinued treatment because of toxicity. No significant difference was observed for disease control rate between methylated and unmethylated patients, although a trend toward improved progression-free survival was reported for methylated patients. Low-dose fotemustine has activity comparable with that of the full-dose regimen, therefore it should be preferred for its greater tolerability. The role of MGMT gene promoter methylation status in relation to sensitivity to fotemustine is still unclear and needs further evaluation in future clinical trials.
authors.affiliation: Division of Medical Oncology, Regina Elena Cancer Institute, Via Elio Chianesi, 53, Rome, Italy. alessandra.fabi@virgilio.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
authors.forename: Antonello
authors.initials: A
authors.lastname: Vidiri
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lanzetta
authors.forename: Mariantonia
authors.initials: M
authors.lastname: Carosi
authors.forename: Stefano
authors.initials: S
authors.lastname: Telera
authors.forename: Marta
authors.initials: M
authors.lastname: Maschio
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Russillo
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Carapella
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; C054368:fotemustine