Toxicity of the topoisomerase I inhibitors

The topoisomerase I inhibitors represent a class of antineoplastic agents with a wide spectrum of activity against malignancies. Currently available topo-isomerase I inhibitors are derivatives of the parent compound, camptothecin. Irinotecan is most active against gastrointestinal (GI) tumours, and has predominantly GI and haematological toxicities. Significant pharmacokinetic variability occurs in patients with hepatic dysfunction, particularly those with glucuronidation pathway deficiencies. The toxicity of topotecan is principally haematological with little extramedullary toxicity. Topotecan is well-tolerated in patients with significant hepatic dysfunction; however, patients with even mild renal insufficiency require significant dose reductions. This article discusses the toxicities of these drugs in detail, including the need for dose adjustments in selected patient populations.