Understandably, cancer drug development and research have recently been largely focused on targeted therapies. Although many of these agents have proven to be incredibly effective and have limited toxicities, cytotoxic chemotherapeutics appear to be undergoing a renaissance.

Although the platinum-based drug cisplatin was first used in the clinic in the 1970s (see the Review on page 573), safer and more effective platinum drugs are still being developed. One of these, oxaliplatin, was approved by the US Food and Drug Administration (FDA) in 2002, and another, satraplatin, is being considered for FDA approval. In addition to the development of new agents, there has been a drive to better understand how tumours develop resistance to platinum agents, in the hope that these resistance mechanisms can be overcome.

Another example is the cytotoxic drug ixabepilone, an epothilone B analogue (Trial Watch, page 569). Like the taxanes (such as docetaxel and paclitaxel), ixabepilone stabilizes microtubules and inhibits mitosis. Positive data from five phase II trials of ixabepilone — four in breast cancer and one in non-small-cell lung cancer (NSCLC) — have recently been reported, and ixabepilone seems to be active in tumours resistant to other cytotoxic therapies, including docetaxel and paclitaxel. Therefore, it might have a place in treating tumours that are resistant to these drugs.

The efficacy of other cytotoxic drugs is also being improved through combination with targeted agents. Bevacizumab, for example, is approved for use in combination with carboplatin and paclitaxel in NSCLC. Although targeted therapies are still likely to cause fewer toxicities than even these new and improved cytotoxic drugs, it is clear that cytotoxics still have a place in modern cancer drug development.