Bioreductive agents: a clinical update

Bioreductive agents are drugs that must undergo reduction to form an active cytotoxic species. The existence within solid tumors of regions of hypoxia offers the possibility of using such bioreductive agents to exert tumor-specific cytotoxicity. The only drug with bioreductive properties that is in routine clinical use in mitomycin C. This is a relatively old drug that has cytotoxicity independent of its bioreductive properties. However, the results of recent randomized clinical trials of mitomycin C in combination with radiotherapy have suggested that its bioreductive properties may play an important part in its activity. EO9 is a new bioreductive agent. Phase I and II clinical trials with EO9 have failed to demonstrate any significant antitumor activity. However, the design of these studies was such that activity based on bioreductive properties may have been difficult to demonstrate. Tirapazamine is the lead compound of a novel class of bioreductive agents. It is currently undergoing extensive clinical evaluation alone, combined with radiotherapy, and in combination with other cytotoxic drugs. Although early results of these trials are encouraging, the results of randomized studies will be required before the true value of this drug can be assessed.