Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome.
OBJECTIVE
To evaluate the predictive impact of chromosome 1p/19q deletions on the response and outcome of progressive low-grade gliomas (LGG) treated with up-front temozolomide (TMZ) chemotherapy.


METHODS
Adult patients with measurable, progressive LGG (WHO grade II) treated with TMZ delivered at the conventional schedule (200 mg/m(2)/day for 5 consecutive days, repeated every 28 days) were retrospectively evaluated for response by central review of MRI-s. Chromosome 1p and 19q deletions were detected by the loss of the heterozygosity technique (LOH).


RESULTS
A total of 149 consecutive patients were included in this retrospective, single center observational study. The median number of TMZ cycles delivered was 14 (range 2 to 30). Seventy-seven patients (53%) experienced an objective response (including 22 [15%] cases of partial response and 55 [38%] cases of minor response), 55 (37%) patients had stable disease, and 14 (10%) had a progressive disease. The median time to maximum tumor response was 12 months (range 3 to 30 months). The median progression-free survival (PFS) was 28 months (95% CI: 23.4 to 32.6). Material for genotyping was available for 86 patients. Combined 1p/19q LOH was present in 42% of the cases and was significantly associated with a higher rate (p = 0.02) and longer objective response to chemotherapy (p = 0.017), and both longer PFS (p = 4.10(-5)) and overall survival (p = 0.04).


CONCLUSIONS
Low-grade gliomas respond to temozolomide and loss of chromosome 1p/19q predicts both a durable chemosensitivity and a favorable outcome.
Kaloshi
G
G
Service de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris Cedex 13, France.
Benouaich-Amiel
A
A
Diakite
F
F
Taillibert
S
S
Lejeune
J
J
Laigle-Donadey
F
F
Renard
M-A
MA
Iraqi
W
W
Idbaih
A
A
Paris
S
S
Capelle
L
L
Duffau
H
H
Cornu
P
P
Simon
J-M
JM
Mokhtari
K
K
Polivka
M
M
Omuro
A
A
Carpentier
A
A
Sanson
M
M
Delattre
J-Y
JY
Hoang-Xuan
K
K
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004252:DNA Mutational Analysis; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide