title: Phase I study of weekly oxaliplatin in relapsed or refractory pediatric solid malignancies.
abstract: OBJECTIVE
  To explore feasibility, maximum-tolerated dose (MTD), and recommended dose (RD) for phase II studies of weekly oxaliplatin for the treatment of relapsed or refractory pediatric solid malignancies.
  
  
  METHODS
  Eligible patients were 6 months to 21 years old, had a diagnosis of a solid malignancy, and had experienced treatment failure with at least two or more previous lines of therapy. The phase I study was multicentric, open-label, and nonrandomized. It foresaw two phases: a dose-escalation phase (comprising six levels) to find the RD and an extension at the RD to evaluate the cumulative toxicity. Oxaliplatin was administered intravenously over 2 hours on days 1, 8, and 15 of a 28-day cycle.
  
  
  RESULTS
  Forty-five patients were enrolled: 29 patients in the dose-escalation phase and 16 patients in the extension at the RD. Median age was 9.5 years (range, 2.8 to 20.0 years) and 7.8 years (range, 1.8 to 19.2 years), respectively. The dose-limiting toxicities during the first treatment cycle were grade 3 (G3) sepsis at 50 mg/m(2), G3 dysesthesia at 90 mg/m(2), and G3 dysesthesia and G3 paresthesia at 110 mg/m(2), thus the MTD and RD was 90 mg/m(2). No case of ototoxicity was reported. Stable disease was reported in seven patients (16.3%), and confirmed partial response was observed in two patients (4.7%), one with neuroblastoma and one with osteosarcoma.
  
  
  CONCLUSIONS
  Oxaliplatin administered in a weekly schedule has an acceptable safety profile, different from cisplatin and carboplatin, and shows activity in children with relapsed or refractory solid tumors, suggesting further investigation in pediatric malignancies.
authors.affiliation: Department of Pediatrics, Institut Gustave-Roussy, Villejuif, France. geoerger@igr.fr
authors.forename: Birgit
authors.initials: B
authors.lastname: Geoerger
authors.forename: François
authors.initials: F
authors.lastname: Doz
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Gentet
authors.forename: Michele
authors.initials: M
authors.lastname: Mayer
authors.forename: Judith
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: Fabienne
authors.initials: F
authors.lastname: Pichon
authors.forename: Pascal
authors.initials: P
authors.lastname: Chastagner
authors.forename: Hervé
authors.initials: H
authors.lastname: Rubie
authors.forename: Didier
authors.initials: D
authors.lastname: Frappaz
authors.forename: Anne
authors.initials: A
authors.lastname: Le Bouil
authors.forename: Sunil
authors.initials: S
authors.lastname: Gupta
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005240:Feasibility Studies; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007223:Infant; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity*; D000077150:Oxaliplatin; D010292:Paresthesia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin