Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: A pediatric oncology group phase II study

Purpose: To determine the response rate of the combination of cyclophospham ide and topotecan in pediatric patients with recurrent or refractory malign ant solid tumors. Patients and Methods: A total of 91 pediatric patients, 83 of whom were ful ly assessable for response and toxicity, received cyclophosphamide (250 mg/ m(2)/dose) followed by topotecan (0.75 mg/m(2)/dose), each given as a 30-mi nute infusion daily for 5 days. All patients received filgrastim (5 mcg/kg) daily until the absolute neutrophil count (ANC) was greater than or equal to 1,500 muL after the time of the expected ANC nadir. Results: A total of 307 treatment courses were given to the 83 fully assess able patients. Responses (complete response plus partial response) were see n in rhabdomyosarcoma (10 of 15 patients), Ewing's sarcoma (six of 17 patie nts), and neuroblastoma (six of 13 patients). Partial responses were seen i n two of 18 patients with osteosarcoma and in one patient with a Sertoli-Le ydig cell tumor. Twenty-three patients had either minor responses (n = 6) o r stable disease (n = 17); the median number of courses administered to pat ients with partial or complete response was six (range, two to 13 courses), and the median administered to those with stable disease was three (range, one to 11 courses). The toxicity of the combination was limited principall y to the hematopoietic system. Of 307 courses, 163 (53%) were associated wi th grade 3 or 4 neutropenia, 84 (27%) with grade 3 or 4 anemia, and 136 (44 %) with grade 3 or 4 thrombocytopenia. Despite the severe myelosuppression, only 34 (11%) of 307 courses were associated with grade 3 or 4 infection. Nonhematopoietic toxicity of grades : 3 was rare and consisted of nausea an d vomiting (two courses), perirectal mucositis (one course), transaminase e levation (one course), and hematuria (two courses). Conclusion: The combination of cyclophosphamide and topotecan is active in rhabdomyosarcoma, neuroblastoma, and Ewing's sarcoma. Stabilization of dise ase was seen in osteosarcoma, although objective responses were rare in thi s disease. The therapy can be given with acceptable hematopoietic toxicity with the use of filgrastim support.