amifostine + topotecan + cytarabine

A multi-agent chemotherapy regimen combining the cytoprotective prodrug amifostine with the antineoplastic small molecules topotecan and cytarabine. Topotecan is a topoisomerase I inhibitor that stabilizes the cleavable complex, causing DNA single-strand breaks and replication-induced double-strand breaks, leading to apoptosis in proliferating leukemia cells. Cytarabine (ara-C) is a pyrimidine antimetabolite that is phosphorylated intracellularly to ara-CTP, which inhibits DNA polymerase and incorporates into DNA, impairing DNA synthesis and repair. Amifostine is a prodrug dephosphorylated by alkaline phosphatase to the active thiol WR-1065, which scavenges free radicals and provides cytoprotection to normal tissues during chemotherapy. Clinical use of topotecan plus cytarabine has been studied in relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), typically with continuous-infusion topotecan and high- or intermediate-dose cytarabine; some protocols include amifostine as a supportive cytoprotectant administered prior to cytotoxic infusions[3][2][1][4].

Other names

ATC regimen