Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients ....

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J Clin Oncol. 2007 Apr 20;25(12):1470-5.

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J Clin Oncol. 2007 Apr 20;25(12):1459-60.

Correlation
between O6-methylguanine-DNA methyltransferase and survival in
inoperable newly diagnosed glioblastoma patients treated with
neoadjuvant temozolomide.
Chinot OL, Barrié M, Fuentes S, Eudes N, Lancelot S, Metellus P, Muracciole X, Braguer D, Ouafik L, Martin PM, Dufour H, Figarella-Branger D.
Unité
de Neuro-Oncologie, Service de Neurochirurgie, Centre Hospitalier
Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, and
Université de la Méditérranée, Faculté de Médecine de Marseille,
Marseille, France.

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 (150 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 O6-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 (17%).

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.