temozolomide + topotecan

Temozolomide + topotecan (TOTEM) is an investigational combination chemotherapy regimen primarily utilized in pediatric oncology and neuro-oncology. The regimen consists of **temozolomide**, an oral alkylating agent that methylates DNA at the O6 and N7 positions of guanine, and **topotecan**, a semi-synthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. The combination is designed to exploit the synergistic activity between DNA-methylating agents and topoisomerase I inhibitors; temozolomide-induced DNA damage is thought to be enhanced by topotecan's inhibition of DNA repair processes, specifically by stabilizing the cleavable complex between topoisomerase I and DNA, leading to lethal double-strand breaks. Both agents exhibit significant blood-brain barrier penetration, making the regimen particularly suitable for central nervous system (CNS) malignancies. It has been extensively studied in academic and cooperative group settings, such as the European Innovative Therapies for Children with Cancer (ITCC) and SIOP Europe Neuroblastoma (SIOPEN) consortia, for the treatment of relapsed or refractory neuroblastoma, primary CNS lymphoma, and brain metastases from solid tumors.

Brand names

HycamtinTemodarTemomedac

Other names

TOTEMTOTEM regimentemozolomide and topotecan