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Temozolomide

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Abstract

▴ Temozolomide is an imidazotetrazine derivative of the alkylating agent dacarbazine. It undergoes chemical conversion to the active species 5-(3-mefhyl-1-triazeno)imidazole-4-carboxamide (MTIC) at physiological pH. Temozolomide exhibits schedule-dependent antineoplastic activity by interfering with DNA replication.

▴ Temozolomide has virtually complete oral bioavailability and crosses the blood-brain barrier. The drug has shown activity against malignant gliomas in humans when administered orally at dosages of 150 to 200 mg/m2 once daily for 5 days, repeated every 28 days.

▴ In 1 noncomparative trial, the objective response rate to temozolomide was 35% in patients with recurrent anaplastic astrocytoma (n = 162) refractory to standard treatment. 46% of patients achieved 6-month progression-free survival, the primary end-point of this trial.

▴ In a randomised, comparative trial with procarbazine in patients with recurrent glioblastoma multiforme, the objective response rate (21 vs 8%) and 6-month survival rate (60 vs 44%) were significantly higher for temozolomide-treated patients (n = 112) compared with procarbazine recipients (n = 113).

▴ Measures of health-related quality of life improved in patients receiving temozolomide for the treatment of recurrent anaplastic astrocytoma or glioblastoma multiforme.

▴ Common Toxicity Criteria grades 3 or 4 myelotoxicity occurred in 5% of temozolomide cycles in 162 patients treated for recurrent anaplastic astrocytoma. No evidence of cumulative haematological toxicity was observed in clinical trials. Other adverse events including nausea, vomiting (controlled by antiemetics), constipation and lethargy were generally mild.

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Karen M. Hvizdos & Karen L. Goa

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  1. Karen M. Hvizdos
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  2. Karen L. Goa
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Correspondence to Karen M. Hvizdos.

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Hvizdos, K.M., Goa, K.L. Temozolomide. Mol Diag Ther 12, 237–243 (1999). https://doi.org/10.2165/00023210-199912030-00006

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