Topotecan and Irinotecan in the Treatment of Pediatric Solid Tumors

Yoshiaki      Tsuchida; Toshiji      Shitara

Abstract

There have been significant advances in the treatment of neuroblastoma and rhabdomyosarcoma, but the clinical results are still poor, especially after tumor relapse. In addition to this, rhabdomyosarcoma does worse if localized tumors occur in unfavorable sites. Therefore, new chemotherapeutic agents have been sought, and the effects of 9- dimethylaminomethyl-10-hydroxycampthothecin (topotecan) and 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonylcamptothecin hydrochloride (irinotecan) were studied preclinically and clinically during the past decade not only in adults but also in children. Irinotecan and topotecan inhibit DNA topoisomerase I, which is an essential nuclear enzyme that relaxes torsionally strained duplex DNA, enabling replication and transcription. These agents were reported to be effective against various human malignancies in adults. Among these camptothecin derivatives, topotecan and irinotecan are the most widely used clinically, and at present irinotecan appears to be more promising in the treatment of childhood solid tumors such as rhabdomyosarcoma and neuroblastoma. The recommended dose and administration schedule differ among clinical trials.. For example, 1-day, 3-day, and 10-day regimens have been used. In the present article, the clinical effectiveness of topotecan and irinotecan with different administration schedules are reviewed in the US, French and Japanese literature, and the authors propose which agent and which administration schedule of these agents are the most effective in the treatment of pediatric solid tumors.

Keywords: topotecan, irinotecan, neuroblastoma, rhabdomyosarcoma, leiomyosarcoma, phase-II trials

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