Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide

被引:172
作者
Chinot, Olivier L.
Barrie, Maryline
Fuentes, Stephane
Eudes, Nathalie
Lancelot, Sophie
Metellus, Philippe
Muracciole, Xavier
Braguer, Diane
Ouafik, L'Houcine
Martin, Pierre-Marie
Dufour, Henry
Figarella-Branger, Dominique
机构
[1] Univ Mediterranee, CHU Timone, Fac Med Marseille, Assistance Publ Hop Marseille,Unite Neurooncol, F-13385 Marseille 05, France
[2] Univ Mediterranee, CHU Timone, Fac Med Marseille, Assistance Publ Hop Marseille,Serv Neurochirurg, F-13385 Marseille 05, France
[3] Univ Mediterranee, CHU Timone, Fac Med Marseille, Assistance Publ Hop Marseille,Serv Pharm, F-13385 Marseille 05, France
[4] Univ Mediterranee, CHU Timone, Fac Med Marseille, Assistance Publ Hop Marseille,Serv Radiotherapie, F-13385 Marseille 05, France
[5] Univ Mediterranee, CHU Timone, Fac Med Marseille, Assistance Publ Hop Marseille,Lab Transfert Oncol, F-13385 Marseille 05, France
[6] Univ Mediterranee, CHU Timone, Fac Med Marseille, Assistance Publ Hop Marseille,Serv Anat Pathol &, F-13385 Marseille 05, France
[7] CNRS, Inst Natl Sante & Rech, Lab Biopathol Adhes & Signalisat, Fac Med Marseille, Marseille, France
关键词
D O I
10.1200/JCO.2006.07.4807
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose This phase II study evaluated the efficacy and safety of a 7-day on/7-day off regimen of temozolomide before radiotherapy (RT) in patients with inoperable newly diagnosed glioblastoma. Patients and Methods Patients received temozolomide (50 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days; 7 days on/7 days off) for up to four cycles before conventional RT (2-Gy fractions to a total of 60 Gy) and for four cycles thereafter or until disease progression. The primary end point was tumor response. Tumor tissue from 25 patients was analyzed for O-6-methylguanine-DNA methyltransferase (MGMT) expression. Results Twenty-nine patients with a median age of 60 years were treated, and 28 were assessable for response. Seven (24%) of 29 patients had a partial response, nine patients (31%) had stable disease, and 12 patients (41%) had progressive disease. Median progression-free survival (PFS) time was 3.8 months, and median overall survival (OS) time was 6.1 months. Patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median, 5.5 v 1.9 months, respectively; P = .009) and OS (median, 16 v 5 months, respectively; P = .003). The most common grade 3 and 4 toxicities were thrombocytopenia (20%) and neutropenia (7%). Conclusion This dose- dense temozolomide regimen resulted in modest antitumor activity with an acceptable safety profile in the neoadjuvant setting, and expression of MGMT correlated with response to temozolomide. However, this treatment approach seems to be inferior to standard concomitant RT plus temozolomide.
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收藏
页码:1470 / 1475
页数:6
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