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lüll Topoisomerase I inhibitors: review and update Rothenberg MLAnn Oncol 1997[Sep]; 8 (9): 837-55This review presents a summary of preclinical and clinical data on the topoisomerase I (topo I) inhibitors that are under clinical development. To date, all of the topo I inhibitors that have been clinically evaluated are analogues of camptothecin, an extract of the Chinese tree Camptotheca acuminata. The therapeutic development of camptothecin was initially limited by its poor solubility and unpredictable toxicity. More recently, a number of water-soluble camptothecin analogues have undergone extensive evaluation and have demonstrated significant clinical activity. These include irinotecan (CPT-II), topotecan, and 9-aminocamptothecin (9-AC). Preliminary data are also reviewed on other camptothecin analogues (GG-211 and DX-8951f), on oral formulations, and on non-camptothecin topoisomerase I inhibitors. The topoisomerase I inhibitors have already demonstrated a broad spectrum of antitumour activity, most probably due to their unique mechanism of action and lack of clinical cross-resistance with existing antineoplastic compounds. The challenge for the next five years is to identify ways to integrate the topo I inhibitors into multidrug and multimodality therapies to achieve optimal antitumour effect, while keeping the side effects of these therapies manageable.|*Topoisomerase I Inhibitors[MESH]|Animals[MESH]|Antineoplastic Agents/*therapeutic use[MESH]|Camptothecin/adverse effects/analogs & derivatives/therapeutic use[MESH]|Clinical Trials as Topic[MESH]|Drug Resistance, Neoplasm[MESH]|Enzyme Inhibitors/*therapeutic use[MESH]|Humans[MESH]|Irinotecan[MESH]|Topotecan/adverse effects/therapeutic use[MESH] |