New drugs in development are initially referred to by letters and number. TH-302 is such a drug that is in clinical development. It is unique in that it is activated under hypoxic conditions, meaning that it works best in tissues that are not getting enough oxygen. Many cancers in the body outgrow their blood supply and are starved for oxygen. TH-302 exploits the activation of a nitroazole prodrug under hypoxic conditions by a process that generate a radical anion prodrug (RP). In the presence of oxygen (normoxia) the radical anion prodrug reacts rapidly with oxygen to generate the original prodrug and superoxide (SO). Under the low oxygen conditions of the hypoxic zones in tumors, however, the radical anion prodrug undergoes further irreversible reductions and goes thorugh other chemical steps, releasing the active drug and an azole derivative (AZ).
It is a promising drug. In March of 2012, European Commission has granted Orphan Drug Designation for TH-302. An international, randomized, controlled Phase 3 clinical trial was initiated in September 2011, and is being conducted in partnership with the Sarcoma Alliance for Research through Collaboration (SARC). The trial is designed to enroll 450 patients with metastatic or locally advanced unresectable soft tissue sarcoma.
With data from over 500 patients to date, TH-302 is currently being evaluated in a controlled Phase 2 clinical trial in patients with advanced pancreatic cancer. Results of phase I trials have been encouraging. University of Texas at San Antonio initiated a clinical trial of TH-302 in combination with bevacizumab in patients with recurrent high grade astrocytoma including glioblastoma.
Until more information is published and assessed, TH-302 remains an investigational agent but one with great promise.
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