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 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). 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.
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 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). 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.
Authors: Jai Woong Seo; JooChuan Ang; Lisa M Mahakian; Sarah Tam; Brett Fite; Elizabeth S Ingham; Janine Beyer; John Forsayeth; Krystof S Bankiewicz; Ting Xu; Katherine W Ferrara Journal: J Control Release Date: 2015-10-05 Impact factor: 9.776
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Authors: Christina K Speirs; Misun Hwang; Sungjune Kim; Weier Li; Sophia Chang; Vinod Varki; Lauren Mitchell; Stephen Schleicher; Bo Lu Journal: Am J Cancer Res Date: 2010-09-30 Impact factor: 6.166
Authors: P O Carminati; F S Donaires; M M Marques; E A Donadi; G A S Passos; E T Sakamoto-Hojo Journal: Mol Biol Rep Date: 2013-11-12 Impact factor: 2.316
Authors: Darren Hargrave; Birgit Geoerger; Didier Frappaz; Torsten Pietsch; Lyle Gesner; Laura Cisar; Aurora Breazna; Andrew Dorman; Ofelia Cruz-Martinez; Jose Luis Fuster; Xavier Rialland; Céline Icher; Pierre Leblond; David Ashley; Giorgio Perilongo; Martin Elliott; Martin English; Niels Clausen; Jacques Grill Journal: J Neurooncol Date: 2013-03-04 Impact factor: 4.130