Prospective randomized trial between two doses of granulocyte colony-stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent or refractory solid tumors: A Children's Cancer Group report

Purpose: The objectives of this study were: 1) to compare the time to hematologic recovery (absolute neutrophil count [ANC] greater than or equal to1,000/mm(3) and platelet count greater than or equal to 100,000/mm(3)) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 mug/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [CR] + partial response [PR]) of ICE in children with refractory or recurrent solid tumors. Patients and Methods: From June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m(2) per day x 5), carboplatin (400 mg/m(2) per day x 2), and etoposide (100 mg/m(2) per day x 5) and randomized to receive either 5.0 mug/kg per day or 10.0 mug/kg per day of G-CSF subcutaneously until recovery of ANC to greater than or equal to1,000/mm(3) Results: The incidence of grade 4 neutropenia during the first course was 88%. Median time from the start of chemotherapy to ANC greater than or equal to1,000/mm(3) for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count less than or equal to 20,000/mm(3) during course 1 was 82%. The median time from the start of the course of chemotherapy to platelet recovery greater than or equal to 100,000/mm(3) for all patients during courses 1 and 2 was 27 days. There was no significant difference in the median time of ANC recovery, platelet recovery, or incidence of grade 4 neutropenia; and in the median days of fever and the incidence of infections requiring hospitalization and intravenous antibiotics during courses 1 and 2, there was no significant difference between the two doses of G-CSF. One hundred eighteen patients were evaluated for response to ICE. The overall response rate (CR + PR) in this study was 51% (90% confidence interval, 43%-59%). The CR rate for all diagnostic categories was 27%. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52% and 30%, respectively. Conclusion: In summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27%) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 3 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 mug/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 3 neutropenia developing.