LAUSR

Abstract The currently active, prospective multi-center Head Start 4 (HS4) trial for CNS embryonal tumors differs from prior HS I-III trials by utilizing absolute phagocyte count (APC) as a measure of myeloid recovery instead of absolute neutrophil count. The aim of this study was to determine if utilization of APC resulted in unanticipated treatment-related toxicities during induction chemotherapy for patients enrolled on HS4. Review of the RedCap database was conducted for treatment-related CTCAE grade 3 and 4 toxicities. Data were summarized descriptively. Nonparametric statistical methods were used for comparisons. At the time of this most recent analysis, a total of 180 induction cycles were completed for the 57 patients enrolled. Of the 57 patients, nine voluntarily discontinued therapy after completing a median of three cycles each. These patients had a higher number of documented infections (59% versus 24%, p=0.0004). Veno-occlusive disease (VOD) occurred in five patients, three of whom voluntarily discontinued therapy. Since the protocol amendment utilizing milligram per kilogram dosing for patients less than six years of age, there have been no documented episodes of VOD. The overall toxicities for this cohort were comparable to those reported for induction chemotherapy in HS I-II trials. The toxic death rate is lower for HS4 compared to HS I-II (0.018% versus 4.7–6%) (Chi et al 2004). Other than the high rate of infection, possibly associated with shorter duration of the immediately prior cycles, the use of APC as part of a dose-compression strategy in HS4 does not appear associated with more significant toxicities.