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MALINGNANT GLIOMAS & ITS TREATMENT WITH CHEMOTHERAPEUTIC AGENT – TEMOZOLOMIDE
INTRODUCTION
Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) occur more frequently than other types of primary CNS tumors, having a combined incidence of 5–8/100,000 population. Even with aggressive treatment using surgery, radiation, and chemotherapy, median reported survival is less than 1 year . Temozolomide, a new drug, has shown promise in treating malignant gliomas and other difficult-to-treat tumors. Temozolomide represents a new class of second-generation imidazotetrazine prodrugs that undergo spontaneous conversion under physiological conditions to the active alkylating agent MTIC. Thus, temozolomide does not require hepatic metabolism for activation .
Interest in temozolomide as an antitumor agent derives from its broad-spectrum antitumor activity in tumor models in mice . In vitro, temozolomide has demonstrated schedule-dependent antitumor activity against a variety of malignancies, including glioma, metastatic melanoma, and other difficult-to-treat cancers . In preclinical studies, temozolomide demonstrated distribution to all tissues, including penetration into the CNS; relatively low toxicity compared with its parent compound, mitozolomide; and antitumor activity against a broad range of tumor types, including glioma, melanoma, mesothelioma, sarcoma, lymphoma, leukemia, and carcinoma of the colon and ovary . Its demonstrated ability to cross the blood-brain barrier is of special interest with respect to its activity in CNS tumors .
In Phase 1 and 2 clinical studies conducted by the CRC (London, United Kingdom), temozolomide was absorbed rapidly, exhibited 100% p.o. bioavailability within 1–2 h of administration, and demonstrated antineoplastic activity in recurrent high-grade glioma, melanoma, and mycosis fungoides . Results of these trials showed that when temozolomide is administered p.o. once daily for 5 days in a 4-week cycle, it is well tolerated, producing mild-to-moderate toxicity that is both predictable and easily managed. The results also confirmed the ability of temozolomide to penetrate the CNS and indicated that temozolomide has considerable potential in treating gliomas and improving the QOL of patients with glioma . Additional Phase 1 studies have confirmed these results and have extended these observations to pediatric patients .
Temozolomide has been evaluated in a number of Phase 2 and 3 clinical trials for the treatment of glioblastoma multiforme, anaplastic astrocytoma, and malignant metastatic melanoma—malignancies for which there are no satisfactory therapies. On the basis of the results of these studies, temozolomide has been approved in the European Union for the treatment of patients with glioblastoma multiforme showing progression or recurrence after standard therapy. Recently, temozolomide received accelerated approval from the FDA for treatment of adult patients with anaplastic astrocytoma who have relapsed after treatment that included a nitrosurea drug (BCNU or CCNU) and procarbazine. Studies are under way to evaluate the combination of temozolomide with other chemotherapeutic agents and biochemotherapy in the treatment of malignant glioma and metastatic melanoma, respectively. This article reviews the mechanism of action of temozolomide as an anticancer agent and summarizes the most recent clinical studies of temozolomide for the treatment of malignant gliomas.
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Peter griffin vs stan smith vs homer simpson?
which of them is ur favourite character and y?
http://youtube.com/watch?v=Fd5PFapT_Ps-p... griffin
Peter griffin
Griffin Smith "Don't Go Breaking My Heart" Duet
