Irinotecan

Other camptothecins under investigation include irinotecan, a prodrug that undergoes enzymatic conversion to the biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (Garcia-Carbonero and Supko 2002). Irinotecan has shown efficacy in pre-clinical studies (Thompson et al. 1997; Komuro et al. 1994; Vassal et al. 1996; Shitara et al. 2003) and produced responses in refractory neuroblastoma (Shitara et al. 2003; Furman et al. 1999). Whereas the predominant toxicity of topotecan is myelosuppression, that of irinotecan is diarrhea (Furman et al. 1999; Rowinsky and Verweij 1997). It is usually adminis-

tered intravenously, but trials of oral irinotecan are currently underway. As mentioned above, laboratory studies in neuroblastoma cell lines suggest that lines which are resistant to either etoposide or topotecan are also likely to be resistant to irinotecan (Keshelava et al. 2000b), although another study showed that irinotecan was effective in a xenograft model of neuroblastoma that was resistant to etoposide (Vassal et al. 1996). This drug has also been extensively studied in adult tumors, both alone and in combination with other chemotherapy. It has not yet been shown in human studies of neuroblastoma whether it is non-cross-resistant or in any way more advantageous than topotecan. Other camptothecin analogues are in various stages of clinical development, including 9-aminocamptothecin, 9-nitrocamptothecin, 7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy-20(S)-camptothecin, exatecan mesylate, and karen-itecin (Garcia-Carbonero and Supko 2002).

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