Fabi Alessandra, Metro Giulio, Russillo Michelangelo, Vidiri Antonello, Carapella Carmine Maria, Maschio Marta, Cognetti Francesco, Jandolo Bruno, Mirri Maria Alessandra, Sperduti Isabella, Telera Stefano, Carosi Mariantonia, Pace Andrea
Division of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy.
BMC Cancer. 2009 Mar 31;9:101. doi: 10.1186/1471-2407-9-101.
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.
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.
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/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.
在复发性恶性胶质瘤（MGs）中，采用常规给药方案（100mg/m²，每周1次，连续3周，随后在5周休息期后每3周给药1次）使用福莫司汀时，血液学毒性发生率较高。此外，在临床环境中从未探讨过O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化状态对福莫司汀活性的影响。
40例复发性预处理MG患者被确定接受剂量范围为65mg/m²至100mg/m²的福莫司汀治疗。根据接受的福莫司汀剂量将患者分为3组，A组接受的剂量最低，C组接受的剂量最高。成功对19例患者的肿瘤组织进行了MGMT启动子甲基化分析。
总体而言，20%的患者对治疗有反应，疾病控制率（DCR，反应加病情稳定）为47.5%。A组和B组的反应率分别为40%和26.5%，而C组的相应值为10%。在19例患者中，发现12例MGMT启动子甲基化，其中观察到DCR为66.5%。所有7例MGMT启动子未甲基化的患者对福莫司汀均病情进展。
65 - 75mg/m²（诱导期）随后75 - 85mg/m²（维持期）的低剂量福莫司汀具有与常规给药方案相当的活性。通过测定MGMT启动子甲基化状态，可能识别出更有可能从福莫司汀化疗中获益的患者。
