Clinical Development of Topoisomerase-Interactive Drugs

    January 1994 in “ Advances in pharmacology ”
    Franco M. Muggia, Howard A. Burris
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    TLDR New drugs targeting DNA enzymes show promise for cancer treatment but have side effects like immune system suppression and hair loss.
    The document from 1994 reviews the clinical development of topoisomerase-interactive drugs, particularly those targeting topoisomerase I and II, which are crucial enzymes in DNA replication and repair. It discusses the historical use of drugs like doxorubicin and the reintroduction of camptothecin derivatives such as topotecan and CPT-11 into clinical trials after initial setbacks due to toxicity. The paper highlights the potential of these drugs in treating various cancers, with topotecan showing activity against tumor cell lines and CPT-11 exhibiting significant antitumor activity in preclinical models. The dose-limiting toxicities for topotecan were myelosuppression and alopecia, while CPT-11 caused neutropenia and diarrhea. The document also explores the possibility of combining topoisomerase I and II inhibitors and emphasizes the need for further empirical testing to optimize their clinical use. However, the number of patients involved in the studies and specific response rates were not provided in the summary.
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