Dose-dense temozolomide regimens: antitumor activity, toxicity, and immunomodulatory effects.

摘要: Temozolomide is an oral alkylating agent with established antitumor activity in patients primary brain tumors and melanoma. The originally approved temozolomide dosing regimen 150 to 200 mg/m(2) per day (Days 1 5 every 28-day cycle [5 of 28 days]). However, extended regimens (eg, 7 14 days, 21 6 8 weeks, or continuously daily) allow for administration a higher cumulative dose have been shown deplete O(6)-methylguanine-DNA methyltransferase, which may enhance cytotoxic activity. This article reviews efficacy safety data from studies that investigated dose-dense recurrent glioma advanced metastatic clinical benefits these compared the standard yet be established. Although toxicity profile generally similar regimen, it associated increased incidence severity lymphocytopenia. management temozolomide-associated lymphodepletion potential risks are discussed. Preclinical evidence suggests host immune response tumor-associated antigens and/or immunotherapy overcome tumor-mediated immunosuppression. Further exploring implications warranted.