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

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Abstract
The objectives of this study were[colon] 1) to compare the time to hematologic recovery (absolute neutrophil count [lsqb]ANC[rsqb] [ge]1,000/mm3 and platelet count [ge]100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 [mgr]g/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [lsqb]CR[rsqb] [plus] partial response [lsqb]PR[rsqb]) of ICE in children with refractory or recurrent solid tumors. From June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m2 per day x 5), carboplatin (400 mg/m2 per day x 2), and etoposide (100 mg/m2 per day x 5) and randomized to receive either 5.0 [mgr]g/kg per day or 10.0 [mgr]g/kg per day of G-CSF subcutaneously until recovery of ANC to [ge]1,000/mm3. The incidence of grade 4 neutropenia during the first course was 88[percnt]. Median time from the start of chemotherapy to ANC [ge]1,000/mm3 for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count [le]20,000/mm3 during course 1 was 82[percnt]. The median time from the start of the course of chemotherapy to platelet recovery [ge]100,000/mm3 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 [plus] PR) in this study was 51[percnt] (90[percnt] confidence interval, 43[percnt][ndash]59[percnt]). The CR rate for all diagnostic categories was 27[percnt]. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52[percnt] and 30[percnt], respectively. In summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27[percnt]) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 4 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 [mgr]g/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 4 neutropenia developing.