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Cancer Research
Year: 2009  |  Volume: 69  |  Issue: 11  |  Page No.: 4742 - 4749

Crystalline Camptothecin-20(S)-O-Propionate Hydrate:A Novel Anticancer Agent with Strong Activity against 19 Human Tumor Xenografts

Z Cao, A Kozielski, X Liu, Y Wang, D Vardeman and B. Giovanella    


To find a more effective and less toxic chemotherapeutic agent, we have successfully prepared crystalline camptothecin-20(S)-O-propionate hydrate (CZ48) by reacting camptothecin with propionic anhydride using concentrated sulfuric acid as catalyst. The biological effectiveness of this new anticancer agent was evaluated by using xenografts of human cancers in nude mice as the testing models. The extensive treatment of 21 human tumors with various dose levels of CZ48 has shown that this agent is highly effective against many different human tumors tested with a striking lack of toxicity. Of the 21 human tumor lines tested, 9 regressed, 5 were <10% of the control, 3 were <20%, and 2 were <40%. Two tumors did not respond. The total response rate was 90% (19 of 21). No toxicity was observed in mice. The effective doses required to achieve the positive response varied from 100 to 1,000 mg/kg/d depending on the tumors. The maximum tolerated dose was not reached because of the nontoxic nature of the drug in mice. Thus, this compound has a much wider therapeutic index compared with that of the existing anticancer drugs currently in use. [Cancer Res 2009;69(11):4742–9]

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