Phase II study of gemcitabine in children with solid tumors of mesenchymal and embryonic origin.

The therapeutic benefit and side-effect profile of gemcitabine in adults with relapsed solid tumors is well known. So far, few data are available about its significance in pediatric relapsed solid tumors. To determine the efficacy and tolerability of gemcitabine in children, the drug was administered by intravenous short-term infusion over 30 min at a dose of 1200 mg/m2 weekly for 3 weeks as one cycle in children with relapsed solid tumor of embryonic or mesenchymal origin. From May 2003 to September 2004, 14 male and six female patients (2-23, median 15.8 years) were recruited for this prospective open-label phase II study (two-step Simon design). The patients suffered from rhabdomyosarcoma (n=8), Ewing's sarcoma (n=4), osteosarcoma (n=2), neuroblastoma (n=3), hepatoblastoma (n=2) and nephroblastoma (n=1). Median duration of therapy was 27.5 days (7-99), corresponding to 4.0 (2-11) infusions of gemcitabine. Two patients (neuroblastoma and Ewing) had stable disease documented for 69 and 70 days, whereas no objective responses were observed. In 34/94 administered infusions; doses had to be reduced or omitted for grade 3-4 hematotoxicity. Minimal activity was observed in this cohort of children with a wide spectrum of mesenchymal and embryonic tumors. Given the relatively low dose of gemcitabine administered, this study does not exclude the possibility of activity at higher doses. Secondly, the tolerability of gemcitabine in children was consistent with that expected in adults. For further studies in this population, we recommend the use of gemcitabine in combination with other agents.