BACKGROUND: Patients with relapsed or refractory Ewing sarcoma have a poor outcome with conventional therapies. Cytarabine decreases EWS/FLI1 protein levels in Ewing sarcoma cells and has demonstrated preclinical activity against Ewing sarcoma in vitro and in vivo. The purpose of this phase II clinical trial was to estimate the response rate of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma. PROCEDURE: Patients with a histologic diagnosis of Ewing sarcoma were eligible if they were <30 years of age, had relapsed or refractory measurable disease, and met standard organ function requirements. Patients received cytarabine 500 mg/m(2)/dose intravenously over 2 hr every 12 hr for 10 doses with cycles repeated every 21 days. Response was assessed according to RECIST criteria. RESULTS: Ten patients (median age 20 years; 7 males) were treated. Only five patients had documented EWS/FLI1 translocated tumors. No objective responses were seen. One patient had stable disease for 5 cycles before developing progressive disease. All patients evaluable for hematologic toxicity developed grade 4 neutropenia and thrombocytopenia during protocol therapy. Patients were not able to receive therapy according to the planned 21-day cycles, with a median interval of 26.5 days. CONCLUSIONS: Cytarabine at the dose and schedule utilized in this trial resulted in hematologic toxicity that limited delivery of this therapy. This regimen also had minimal activity in this patient population.
BACKGROUND:Patients with relapsed or refractory Ewing sarcoma have a poor outcome with conventional therapies. Cytarabine decreases EWS/FLI1 protein levels in Ewing sarcoma cells and has demonstrated preclinical activity against Ewing sarcoma in vitro and in vivo. The purpose of this phase II clinical trial was to estimate the response rate of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma. PROCEDURE: Patients with a histologic diagnosis of Ewing sarcoma were eligible if they were <30 years of age, had relapsed or refractory measurable disease, and met standard organ function requirements. Patients received cytarabine 500 mg/m(2)/dose intravenously over 2 hr every 12 hr for 10 doses with cycles repeated every 21 days. Response was assessed according to RECIST criteria. RESULTS: Ten patients (median age 20 years; 7 males) were treated. Only five patients had documented EWS/FLI1 translocated tumors. No objective responses were seen. One patient had stable disease for 5 cycles before developing progressive disease. All patients evaluable for hematologic toxicity developed grade 4 neutropenia and thrombocytopenia during protocol therapy. Patients were not able to receive therapy according to the planned 21-day cycles, with a median interval of 26.5 days. CONCLUSIONS:Cytarabine at the dose and schedule utilized in this trial resulted in hematologic toxicity that limited delivery of this therapy. This regimen also had minimal activity in this patient population.
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Authors: Christy L Osgood; Nichole Maloney; Christopher G Kidd; Susan Kitchen-Goosen; Laura Segars; Meti Gebregiorgis; Girma M Woldemichael; Min He; Savita Sankar; Stephen L Lessnick; Min Kang; Malcolm Smith; Lisa Turner; Zachary B Madaj; Mary E Winn; Luz-Elena Núñez; Javier González-Sabín; Lee J Helman; Francisco Morís; Patrick J Grohar Journal: Clin Cancer Res Date: 2016-03-15 Impact factor: 12.531