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. Patients and Methods: Hea...

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Published in:Anticancer research 2009-10, Vol.29 (10), p.4275-4279
Main Authors: ZUSTOVICH, Fable, LOMBARDI, Giuseppe, DELLA PUPPA, Alessandro, ROTILIO, Antonino, SCIENZA, Renato, PASTORELLI, Davide
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Brain Neoplasms - drug therapy
Cisplatin - administration & dosage
Cisplatin - adverse effects
Dacarbazine - administration & dosage
Dacarbazine - adverse effects
Dacarbazine - analogs & derivatives
Drug Resistance, Neoplasm
Female
Glioma - drug therapy
Humans
Male
Medical sciences
Middle Aged
Neurology
Tumors
Tumors of the nervous system. Phacomatoses
Young Adult
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Summary: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. Patients and 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 achivied, 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). Conclusion: 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.
ISSN:0250-7005
1791-7530