The Potential Role of Topotecan in the Treatment of Pediatric and Adult Soft-Tissue Sarcomas

Abstract

Topotecan, a novel topoisomerase I inhibitor, has shown to be active in a variety of solid tumors. Studies have also investigated the potential role of topotecan in soft-tissue sarcomas. Sarcomas represent a heterogeneous group of neoplasms with more than 50 different histological subtypes. While soft-tissue sarcomas account for only 0.7% of all cancers in the adult, they are much more common in children. Current standard therapy consists of combined modality treatment including surgery followed by radiotherapy for localized diseases. In metastatic disease, combination chemotherapy with doxorubicin and ifosfamide, as the two most active agents, will achieve response rates in 25–35% of patients. However, no prolongation of survival has been achieved thus far as compared to doxorubicin monotherapy. Topotecan has shown to be active against sarcoma cell lines in vitro, even in cell lines expressing common mechanisms of resistance such as MDR. First results from clinical trials have indicated a limited activity with 10% response rates of topotecan when given as a 30-min infusion over 5 days. Based on several preclinical trials suggesting a higher activity of continuous infusion of topotecan, studies are underway examining the efficacy of this approach. Combination chemotherapy is an established therapy in children suffering from soft-tissue sarcomas. With a response rate of 46% in children with rhabdomyosarcoma, topotecan seems to be very effective against this disease. Therefore, studies are currently ongoing in order to compare topotecan to standard therapy and to evaluate topotecan as part of the established combination regimens. These results as well as further studies are clearly needed in order to define a potential role of topotecan in the treatment of adult and pediatric soft-tissue sarcomas.