title: A phase I clinical, pharmacologic, and biologic study of thrombopoietin and granulocyte colony-stimulating factor in children receiving ifosfamide, carboplatin, and etoposide chemotherapy for recurrent or refractory solid tumors: a Children's Oncology Group experience.
abstract: OBJECTIVE
  Ifosfamide, carboplatin, and etoposide (ICE) are associated with grade III/IV dose-limiting thrombocytopenia. The Children's Oncology Group conducted a phase I dose escalation, pharmacokinetic, and biological study of recombinant human thrombopoietin (rhTPO) after ICE in children with recurrent/refractory solid tumors (CCG-09717) to assess the toxicity and maximum tolerated dose of rhTPO administered at 1.2, 2.4, or 3.6 microg/kg per dose.
  
  
  METHODS
  Children received ifosfamide 1,800 mg/m2 on days 0 to 4, carboplatin 400 mg/m2 on days 0 to 1, and etoposide 100 mg/m2 on days 0 to 4. rhTPO was administered i.v. on days +4, +6, +8, +10, and +12 at 1.2, 2.4, or 3.6 microg/kg per dose.
  
  
  RESULTS
  rhTPO was well tolerated and maximum tolerated dose was not reached. Median time to platelet recovery > or =100,000/microL of rhTPO at 1.2, 2.4, and 3.6 microg/kg/d was 24 days (22-24 d), 25 days (23-29 d), and 22 days (16-37 d), respectively. Patients required a median of 2 days of platelet transfusions (0-7 days). Mean (+/- SD) rhTPO maximum serum concentrations were 63.3 +/- 9.7 and 89.3 +/- 15.7 ng/mL and terminal half-lives were 47 +/- 13 and 64 +/- 42 hours after 2.4 and 3.6 microg/kg/d, respectively. There was a significant increase in colony-forming unit megakaryocyte upon WBC count recovery.
  
  
  CONCLUSIONS
  rhTPO was well tolerated. Time to hematologic recovery and median number of platelet transfusions seem to be improved compared with historical controls receiving ICE + granulocyte colony-stimulating factor (CCG-0894).
authors.affiliation: Children's National Medical Center, George Washington University, Washington, DC, USA. aangiolillo@cnmc.org
authors.forename: Anne L
authors.initials: AL
authors.lastname: Angiolillo
authors.forename: Virginia
authors.initials: V
authors.lastname: Davenport
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Bonilla
authors.forename: Carmella
authors.initials: C
authors.lastname: van de Ven
authors.forename: Janet
authors.initials: J
authors.lastname: Ayello
authors.forename: Olga
authors.initials: O
authors.lastname: Militano
authors.forename: Langdon L
authors.initials: LL
authors.lastname: Miller
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: Gregory
authors.initials: G
authors.lastname: Reaman
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D013926:Thrombopoietin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D013926:Thrombopoietin; D016190:Carboplatin; D007069:Ifosfamide