Thiotepa (DB04572): A Comprehensive Pharmacological and Clinical Monograph

I. Introduction

Thiotepa is a seminal organophosphorus alkylating agent with a rich and evolving clinical history that spans more than six decades.[1] Originally synthesized in the early 1950s for applications in the textile industry, its potent effects on rapidly dividing cells were quickly recognized, leading to its investigation as a chemotherapeutic agent.[3] The drug's core antineoplastic mechanism is rooted in its ability to form highly reactive ethylenimine radicals that induce covalent cross-links within the DNA double helix, a non-cell-cycle-specific action that disrupts cellular replication and triggers apoptosis.[1] This fundamental mechanism underpins its broad-spectrum activity against a variety of malignancies.

In the landscape of modern oncology, Thiotepa holds a dual identity. It maintains its historical role in the palliative treatment of several solid tumors, including adenocarcinoma of the breast and ovary, and superficial papillary carcinoma of the bladder.[1] However, its most critical contemporary application is as a high-dose conditioning agent prior to hematopoietic stem cell transplantation (HSCT). In this setting, its potent myelosuppressive and immunosuppressive properties are leveraged to eradicate residual malignancy and facilitate engraftment, making it a cornerstone of treatment for numerous hematologic and central nervous system (CNS) cancers.[1]