Phase II study of 21 day continuous intravenous infusion (CIVI) topotecan for recurrent pediatric solid tumors: A Children’s Oncology Group Study (COG A09713)

Abstract

8523 Background: The anti-tumor activity of topotecan is schedule-dependent, with protracted administration having the greatest pre-clinical efficacy. We determined the response rate of selected recurrent pediatric solid tumors to a 21-day CIVI of topotecan. Methods: Patients with Ewing’s sarcoma family of tumors (ESFT), osteosarcoma (OS), soft tissue sarcomas (STS), medulloblastoma (MB)/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 CIVI for 21 consecutive days, followed by 7 days without therapy prior to response assessment. Courses could be repeated every 28 days. Results: 55 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, 3 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: Although responses were observed in ESFT, no activity was seen in other sarcoma strata. Further development of prolonged topotecan CIVI for pediatric sarcomas is not warranted. No significant financial relationships to disclose.