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This combination chemotherapy regimen consists of docetaxel, a second-generation taxoid, and temozolomide, an oral alkylating agent. Docetaxel functions as a microtubule stabilizer, binding to tubulin to prevent depolymerization, which effectively arrests the cell cycle and inhibits cell division. Temozolomide is a prodrug that undergoes spontaneous hydrolysis at physiological pH to its active metabolite, MTIC, which delivers a methyl group to DNA (primarily at the O6 and N7 positions of guanine), leading to DNA damage and subsequent apoptosis. This specific combination was investigated by The Cleveland Clinic in a Phase I dose-escalation study for patients with refractory metastatic solid tumors to determine the maximum tolerated dose and toxicity profile of the dual-agent approach.
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