temozolomide + thiotepa

Temozolomide + thiotepa is a combination of two alkylating agents used primarily in high-dose chemotherapy regimens for the treatment of recurrent or refractory malignant brain tumors, including high-grade glioma, medulloblastoma/primitive neuro-ectodermal tumor (PNET), central nervous system germ cell tumors, and ependymomas. Temozolomide is an oral imidazotetrazine prodrug that undergoes spontaneous hydrolysis to form the active compound MTIC, which methylates DNA at the O6 and N7 positions of guanine residues, leading to DNA damage and tumor cell death. Thiotepa is a polyfunctional alkylating agent that crosslinks DNA strands by transferring alkyl groups to nucleophilic sites on DNA bases, resulting in inhibition of DNA replication and transcription. The combination exploits their non-overlapping toxicity profiles and synergistic antitumor effects. This regimen is often used with autologous hematopoietic stem cell rescue (AHCR) due to its myeloablative potential[1][2][3][5].