DDEL-02. DECREASED TOXICITY OF CONVENTIONAL DOSE CHEMOTHERAPY UTILIZING BODY WEIGHT INSTEAD OF BODY SURFACE AREA FOR DOSING IN YOUNG CHILDREN <6 YEARS OLD ENROLLED ON THE "HEAD START" 4 CLINICAL TRIAL. (4th December 2020)

• Record Type: Journal Article
• Authors: Dhall, Girish; Khatib, Ziad; Maher, Ossama; Blue, Megan; Harmon, Myeshia; Patel, Parth; Finlay, Jonathan
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 3
• Page Start: iii283
• Page End: iii284
• Publication Date: 2020-12-04
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa222.037
• 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. To be consistent with Children&#39;s Oncology Group (COG) guidelines, body surface area (BSA) was used to dose chemotherapeutics in children &gt;3 years old enrolled on &quot;Head Start&quot; 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/m 2 ). 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/m 2 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 &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 &lt;6 years of age with intensive induction chemotherapy by BSA.