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Metabolism of drugs in infants and young children is significantly different from older individuals due to differences in distribution, protein-binding capacity, hepatic metabolism and renal excretion. To be consistent with Children’s Oncology Group (COG) guidelines, body surface area (BSA) was used to dose chemotherapeutics in children &amp;gt;3 years old enrolled on “Head Start” 4 clinical trial (HS 4). Four of 30 patients enrolled on HS 4 developed sinusoidal obstruction syndrome (SOS) while receiving induction chemotherapy with cisplatin, etoposide, vincristine, cyclophosphamide and high-dose methotrexate using BSA for dosing (mg/m2). Patients #1 and #2 were both 2-years old at diagnosis, received and tolerated the first two cycles with mg/kg dosing uneventfully, then turned 3-years old and received cycle #3 with mg/m2 dosing as per protocol guidelines, and developed SOS. Patient #3 was 3-years old at diagnosis, received induction chemotherapy with mg/m2 dosing, and developed SOS during the very first cycle. Patient #4 was 4-years old at diagnosis and received all 3 induction cycles with mg/m2 dosing, developed serious nephrotoxicity during cycle #1 followed by SOS during cycle #3. The HS 4 trial was amended and reopened after external, independent Data Safety Monitoring Board review to dose all chemotherapy drugs in children &amp;lt;6 years old with mg/kg dosing instead of BSA. None of 75 patients enrolled since the amendment developed SOS during induction. These data suggest using caution while dosing young children &amp;lt;6 years of age with intensive induction chemotherapy by BSA.

neuro-oncology

DDEL-02. DECREASED TOXICITY OF CONVENTIONAL DOSE CHEMOTHERAPY UTILIZING BODY WEIGHT INSTEAD OF BODY SURFACE AREA FOR DOSING IN YOUNG CHILDREN &amp;lt;6 YEARS OLD ENROLLED ON THE “HEAD START” 4 CLINICAL TRIAL