title: Phase 1 study of an oxaliplatin and etoposide regimen in pediatric patients with recurrent solid tumors.
abstract: BACKGROUND
  The combination of a platinating agent and etoposide has induced responses in various pediatric tumors. The study estimated the maximum tolerated dose (MTD) of an oxaliplatin and etoposide regimen in children with recurrent solid tumors.
  
  
  METHODS
  Oxaliplatin was administered on Day 1 and etoposide on Days 1 to 3 of each 21-day course. Cohorts of 3 to 6 patients were enrolled at 3 dose levels: 1) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of 75 mg/m(2), 2) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of 100 mg/m(2), and 3) oxaliplatin at a dose of 145 mg/m(2) and etoposide at a dose of 100 mg/m(2). Calcium and magnesium infusions were used at dose level 3 in an attempt to escalate the oxaliplatin dose past the single-agent MTD.
  
  
  RESULTS
  The 16 patients received a total of 63 courses. At dose level 1, dose-limiting epistaxis, neuropathy, and neutropenia occurred in 1 of 6 patients. No dose-limiting toxicity (DLT) occurred at dose level 2 (n = 6). At dose level 3, 2 of 4 patients experienced dose-limiting neutropenia; none experienced grade 3 or 4 acute neuropathy. Six patients required prolongation of the oxaliplatin infusion because of acute sensory neuropathy. Responses were observed in patients with medulloblastoma (1 complete response) and pineoblastoma (1 partial response); 3 others with atypical teratoid rhabdoid tumor, ependymoma, and soft tissue sarcoma had prolonged disease stabilization.
  
  
  CONCLUSIONS
  The MTD of this regimen was found to be oxaliplatin at a dose of 130 mg/m(2) given on Day 1 and etoposide at a dose of 100 mg/m(2)/d given on Days 1 to 3. Neutropenia was found to be the DLT. Calcium and magnesium infusions did not allow escalation of the oxaliplatin dose. The combination was well-tolerated and demonstrated antitumor activity.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. lisa.mcgregor@stjude.org
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McGregor
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Spunt
authors.forename: Victor M
authors.initials: VM
authors.lastname: Santana
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ward
authors.forename: Amy
authors.initials: A
authors.lastname: Watkins
authors.forename: Fred H
authors.initials: FH
authors.lastname: Laningham
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Furman
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D012008:Recurrence
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005047:Etoposide