PHRM-05. INCREASED TOXICITY OF CONVENTIONAL DOSE CHEMOTHERAPY UTILIZING BODY SURFACE AREA FOR DOSING IN INFANTS AND YOUNG CHILDREN ENROLLED ON THE "HEAD START" 4 CLINICAL TRIAL. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Dhall, Girish; Khatib, Ziad; Maher, Ossama; Jaeger, Megan; Harmon, Myeshia; Haley, Kelley; Rushing, Teresa; Finlay, Jonathan
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i157
• Page End: i157
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.583
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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. Body surface area (BSA) is used to dose chemotherapeutics in older children; however, this is inappropriate for infants and young children since it does not take into account the differences in extracellular water distribution. We describe four cases of sinusoidal obstruction syndrome (SOS) that occurred in young children while receiving induction chemotherapy with cisplatin, etoposide, vincristine, cyclophosphamide and high-dose methotrexate on the "Head Start (HS)" 4 clinical trial 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. In contrast, none of the 40 patients treated on HS II protocol with identical chemotherapy regimen, but with mg/kg dosing, developed SOS. Caution should be exercised when dosing young children between 3-6 years of age by BSA. The HS 4 trial was amended and reopened after external, independent DSMB review to dose all chemotherapy drugs in children <6 years old with mg/kg dosing.