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Expert Opin Investig Drugs. 2011 Nov;20(11):1565-74. doi: 10.1517/13543784.2011.617740.

Preclinical and clinical activity of the topoisomerase I inhibitor, karenitecin, in melanoma.

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University of California, Department of Medicine, San Francisco, CA , USA.



This review covers the preclinical and clinical activity of the novel camptothecin analog, karenitecin, in melanoma.


While the camptothecins are widely used antitumor agents that inhibit topoisomerase I, their utility is limited by instability, high interpatient variability and the development of drug resistance. Karenitecin was rationally designed to overcome these limitations. The authors review the data on karenitecin in preclinical models and in clinical trials in melanoma using studies published in Medline and reports presented at AACR and ASCO.


Karenitecin shows activity in melanoma, both as a single agent and in combination. In adverse prognostic factor melanoma, karenitecin showed prolonged disease stabilization in 34% of patients. Because preclinical studies suggested a synergistic interaction between karenitecin and HDAC inhibitors, a schedule-specific combination Phase I-II trial of valproic acid and karenitecin was carried out in heavily pretreated melanoma patients which showed a benefit rate in 47% patients with acceptable toxicity. The treatment for melanoma is in rapid transition and genomic profiling is now an integral part, and hence the optimal use of karenitecin in melanoma should be re-evaluated with regard to specific mutational status.

[Indexed for MEDLINE]

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