Refractory anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV) are primary malignant brain tumours with poor prognosis and limited treatment options. Despite considerable genetic heterogeneity, these tumours often have impaired DNA repair systems, rendering them initially sensitive to alkylating agents, although they invariably develop resistance to these agents over time. Temozolomide is an imidazotetrazine prodrug that is stable at acidic pH but undergoes spontaneous nonenzymatic hydrolysis at neutral or slightly basic pH; these properties allow for both oral and intravenous administration. Following initial hydrolysis, further reactions liberate a highly reactive methyl diazonium cation capable of methylating various residues on adenosine and guanine bases leading to DNA lesions and eventual apoptosis. Temozomolide as an adjunct to radiotherapy followed by maintenance dosing remains the standard of care for both Glioblastoma and refractory anaplastic astrocytoma.
Temozolomide was granted FDA approval on August 11, 1999, as an oral capsule and subsequently on February 27, 2009, as an intravenous injection. It is currently marketed under the trademark TEMODAR® by Merck.
Temozolomide is indicated in adult patients for the treatment of newly diagnosed glioblastoma concomitantly with radiotherapy and for use as maintenance treatment thereafter. It is also indicated for the treatment of refractory anaplastic astrocytoma in adult patients or adjuvant therapy for adults with newly diagnosed anaplastic astrocytoma.
Thomas Jefferson University Cancer Center, Philadelphia, Pennsylvania, United States
UT Southwestern Cancer Center, Dallas, Texas, United States
University of Washington, Seattle, Washington, United States
Bristol Haematology and Oncology Centre, Bristol, England, United Kingdom
Royal Marsden Hospital, Sutton, England, United Kingdom
Christie Hospital, Manchester, England, United Kingdom
CHU de Bordeaux, Bordeaux, Aquitaine, France
Center Eugene Marquis, Rennes, Brittany, France
CHU de Poitiers, Poitiers, Poitou-Charentes, France
Emory University, Atlanta, Georgia, United States
Mayo Clinic, Rochester, Minnesota, United States
Stanford University School of Medicine, Stanford, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Yakima, Washington, United States
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center, Cleveland, Ohio, United States
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