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.
Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi, China
Liuzhou People's Hospital, Liuzhou, Guangxi, China
Liuzhou Worker's Hospital, Liuzhou, Guangxi, China
Istituto Tumori di Napoli - Fondazione G. Pascale, Napoli, Campania, Italy
Huzhou Central Hospital, Huzhou, Zhejiang, China
Ningbo Yinzhou People's Hospital, Ningbo, Zhejiang, China
the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Northwestern University, Chicago, Illinois, United States
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities), Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center, New York, New York, United States
University of Virginia, Charlottesville, Virginia, United States
University of Alabama at Birmingham, Birmingham, Alabama, United States
University of California, San Diego, La Jolla, California, United States
Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, United States
APHP - Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Weill Cornell Medical College, New York, New York, United States
Duke University Medical Center, Durham, North Carolina, United States
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