Topotecan by 21-day continuous infusion in children with relapsed or refractory solid tumors: A Children's Oncology Group study

Purpose. The Children's Oncology Group conducted a phase II trial of 21-day continuous infusion topotecan to determine the response rate in pediatric patients with recurrent or refractory malignant solid tumors. Procedure. Patients with Ewing sarcoma family of tumors (ESFT), osteosarcoma (OS), soft tissue sarcomas (STS), medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), astrocytoma, or neuroblastoma (NB) recurrent or refractory to conventional therapy, measurable disease, and adequate organ function were treated with topotecan 0.3 mg/m²/day by continuous intravenous infusion for 21 consecutive days, followed by 7 days without therapy prior to response assessment. Results. Fifty-five patients were enrolled; two were ineligible, two were removed from protocol therapy prior to evaluation for response, and one was inevaluable for response, leaving 53 and 50 patients evaluable for toxicity and response, respectively. Objective responses were seen in 2/20 patients with ESFT (both partial responses, 4 and 19 courses), 0/10 OS patients, and 0/12 STS patients. There were insufficient patients enrolled to determine the response rate for the MB/PNET, astrocytoma, and NB strata. The most common Grade 3 or 4 toxicities during the first course of therapy were thrombocytopenia (12/53), neutropenia (8/53), and fatigue (7/53). Conclusion. Intravenous topotecan by 21-day continuous infusion is tolerable in pediatric patients with recurrent or refractory solid tumors. Limited activity was seen in ESFT and further development of this topotecan schedule as a single agent is not warranted.