Temozolomide: a milestone in neuro-oncology and beyond?
Temozolomide (Temodal, Temodar), an imidazol derivative, is a second-generation alkylating agent. The orally available prodrug with the capacity of crossing the blood-brain barrier received accelerated US FDA approval in 1999. Three pivotal Phase II trials showed modest activity in the treatment of recurrent anaplastic astrocytoma glioblastoma. In 2005, the FDA and the European Agency for the Evaluation of Medicinal Products approved temozolomide for use in newly diagnosed glioblastoma, in conjunction with radiotherapy, based on an European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Phase III trial. The adverse events associated with temozolomide are mild-to-moderate and generally predictable; the most serious are noncumulative and reversible myelosuppression and, in particular, thrombocytopenia, which occurs in less than 5% of patients. Continuous temozolomide administration is associated with profound CD4-selective lymphocytopenia. Molecular studies have suggested that the benefit of temozolomide chemotherapy is restricted to patients whose tumors have a methylated methylguanine methyltransferase gene promotor and are thus unable to repair some of the chemotherapy-induced DNA damage. Temozolomide is under investigation for other disease entities, in particular lower-grade glioma, brain metastases and melanoma.
Mutter
Nicole
N
Multidisciplinary Oncology Center University of Lausanne Hospitals 46 Rue du Bugnon, 1011 Lausanne, Switzerland. nicole.mutter@chuv.ch
Stupp
Roger
R
D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D020137:Base Pair Mismatch; D001932:Brain Neoplasms / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D012008:Recurrence; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide