A phase II study of cisplatin and temozolomide in heavily pre-treated patients with temozolomide-refractory high-grade malignant glioma.
BACKGROUND
There is pre-clinical evidence of synergism between cisplatin and temozolomide due to higher inhibition of O(6)-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system and in the mechanisms of drug resistance to alkylating agents.


METHODS
Heavily pre-treated patients with temozolomide-refractory high-grade malignant glioma received cisplatin at a dose of 75 mg/m(2) on day 1 and temozolomide at a dose of 150 mg/m(2) on days 1 to 5 every 21 days until progression or major toxicity.


RESULTS
Twenty-four patients were enrolled and a total of 96 cycles were delivered (median for each patient=4). Toxicity was manageable and mostly grade 1-2: haematological, gastroenterological (nausea and vomiting) and fatigue. In patients with glioblastoma, an overall response rate of 29.4% was achieved, with no complete response, and with a disease control rate (responses plus stabilizations) of 64.7%. The median time to progression was 3.8 months (95% confidence interval 2.4-6.8), progression-free survival at 6 months was 28% and overall survival was 7.0 months (95% confidence interval 4.8-11.0).


CONCLUSIONS
The combination of temozolomide and cisplatin is safe and moderately effective in the treatment of heavily pre-treated patients with relapsed high-grade glioma refractory to single-agent temozolomide.
Zustovich
Fable
F
Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy.
Lombardi
Giuseppe
G
Della Puppa
Alessandro
A
Rotilio
Antonino
A
Scienza
Renato
R
Pastorelli
Davide
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D055815:Young Adult
D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide