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etoposide + carboplatin + melphalan + cisplatin + thiotepa

Development stage
Preclinical
Lead developer
Bristol Myers Squibb
Modality
DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous, Intrathecal
01

Overview

This is a high-dose chemotherapy combination regimen consisting of five cytotoxic agents: etoposide, carboplatin, melphalan, cisplatin, and thiotepa. Each drug in this combination is an antineoplastic agent with distinct mechanisms of action targeting DNA synthesis or function. Etoposide inhibits topoisomerase II, leading to DNA strand breaks; carboplatin and cisplatin are platinum-based compounds that form DNA crosslinks and inhibit replication; melphalan is an alkylating agent that causes DNA crosslinking; and thiotepa is also an alkylating agent causing DNA damage. This multi-agent regimen may be used as conditioning therapy prior to autologous stem cell transplantation in patients with high-risk or relapsed cancers such as brain tumors or germ cell tumors. The rationale for combining these drugs lies in their complementary mechanisms of action and non-overlapping toxicity profiles.

02

Targets

TOP2A (DNA topoisomerase II)

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