title: A multi-center phase Ib study of oxaliplatin (NSC#266046) in combination with fluorouracil and leucovorin in pediatric patients with advanced solid tumors.
abstract: BACKGROUND
  Platinum agents have been used for a variety of cancers, including pivotal use in pediatric tumors for many years. Oxaliplatin, a third generation platinum, has a different side effect profile and may provide improved activity in pediatric cancers.
  
  
  METHODS
  Patients 21 years or younger with progressive or refractory malignant solid tumors, including tumors of the central nervous system were enrolled on this multi-center open label, non-randomized Phase 1 dose escalation study. The study used a standard 3 + 3 dose escalation design with 2 dose levels (85 and 100 mg/m(2) ) with an expansion cohort of 15 additional patients at the recommended dose. Patients received oxaliplatin at the assigned dose level and 5-fluorouracil (5-FU) bolus 400 mg/m(2)  followed by a 46-hour 5-FU infusion of 2,400 mg/m(2)  every 14 days. The leucovorin dose was fixed at 400 mg/m(2)  for all cohorts.
  
  
  RESULTS
  Thirty-one evaluable patients were enrolled, 8 at 85 mg/m(2)  and 23 at 100 mg/m(2)  for a total of 121 courses. The median age was 12 years (range 2-19 years). The main toxicities were hematologic, primarily neutrophils and platelets. The most common non-hematologic toxicities were gastrointestinal. Stable disease was noted in 11 patients (54% of evaluable patients) and 1 confirmed partial response in a patient with osteosarcoma.
  
  
  CONCLUSIONS
  The maximum planned dose of oxaliplatin at 100 mg/m(2)  per dose in combination with 5-FU and leucovorin was safe and well tolerated and in this patient population. This combination demonstrated modest activity in patients with refractory or relapsed solid tumor and warrants further study. Pediatr Blood Cancer 2013;60:230-236. © 2012 Wiley Periodicals, Inc.
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Macy
authors.forename: Tracey
authors.initials: T
authors.lastname: Duncan
authors.forename: James
authors.initials: J
authors.lastname: Whitlock
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Jessica
authors.initials: J
authors.lastname: Boklan
authors.forename: Aru
authors.initials: A
authors.lastname: Narendren
authors.forename: Cynthia
authors.initials: C
authors.lastname: Herzog
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Rochelle
authors.initials: R
authors.lastname: Bagatell
authors.forename: Tanya
authors.initials: T
authors.lastname: Trippett
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.forename: Katherine
authors.initials: K
authors.lastname: Rolla
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077150:Oxaliplatin
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil