#temozolomide

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The most common adverse events, nausea and vomiting, can readily be controlled with anti-emetics. Dose-limiting toxicity mainly consists of myelosuppression (mainly grade 3/4 thrombocytopenia with an incidence of 8 to 17% across phase II and observational studies and neutropenia to a lesser extend).14,15 Limiting toxicity usually is evident in the first two treatment cycles. Platelet and neutrophil nadirs occur late in the cycle and recovery can usually be observed within 1-2 weeks. Unlike nitrosureas, treatment with TMZ is not associated with cumulative toxicity. Only very rarely, unpredictable, severe myelosuppression prohibits the continuation of TMZ treatment in responding patients.

TMZ has been an approved drug treatment for patients with high grade gliomas (tumours arising from glial cells) in the UK since 2007. Even though TMZ may cause some side-effects, just as other chemotherapy drugs do, the results of large-scale clinical trials have shown that the possible benefits far outweigh the risks for the treatment of high-grade gliomas. (See our ‘Chemotherapy’ fact sheet for more information). In terms of effectiveness, large-scale clinical trials have shown that TMZ alongside radiotherapy improves average survival for glioblastoma patients compared to those who only receive radiotherapy. Today, TMZ is referred to as the ‘international gold standard’ of treatment as it is the main chemotherapy drug used globally for the treatment of glioblastoma.

Temozolomide (Temodar) is an oral alkylating agent approved by the FDA for use in the first-line treatment of glioblastoma multiforme as well as for recurrent anaplastic astrocytoma.1Alkylating agents are some of the oldest drugs in the chemotherapy arsenal and were originally developed as chemical weapons during the early part of the twentieth century. Their anti-neoplastic aspects were only further investigated after World War II.2 Traditional alkylating agents act by producing DNA cross-linkages, thus inhibiting DNA and cellular replication. Other similarly acting drugs, such as temozolomide, work by methylating DNA, which also results in inhibited DNA and cellular replication.2 All such agents act nonspecifically and affect both cancerous and normal cells alike. However, cancer cells divide more rapidly than normal tissue and thus should be more sensitive to these effects.

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