title: The effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet recovery in breast cancer patients undergoing autologous bone marrow transplantation.
abstract: OBJECTIVE
  To assess the safety and efficacy of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) administered after autologous bone marrow transplantation (ABMT).
  
  
  METHODS
  Two randomized, double-blind, placebo-controlled studies were done. In the phase 1/2 study, 75 breast cancer patients underwent a bone marrow harvest and myeloablative STAMP V chemotherapy and were randomized to receive placebo or one of three doses of PEG-rHuMGDF. In the phase 3 study, 64 patients were randomized to receive placebo or the minimally effective dose of PEG-rHuMGDF. The study drug was administered daily starting on the day of bone marrow infusion until the platelet count was greater than or equal to 50 x 10(9)/L (without transfusion) or for a maximum of 28 days. All patients received 10 microg/kg/day filgrastim starting on day 2 until neutrophil count recovery.
  
  
  RESULTS
  PEG-rHuMGDF appeared to be safe and well tolerated. No significant differences were noted in mortality or disease progression rates. Antibodies to MGDF were not observed. In the phase 1/2 study, the time to platelet recovery to greater than or equal to 20 x 10(9)/L and platelet transfusion requirements were significantly reduced for patients treated with PEG-rHuMGDF compared with placebo (p < 0.05). In the phase 3 study, no significant differences in the kinetics of early thrombopoiesis or platelet transfusions after ABMT were observed.
  
  
  CONCLUSIONS
  PEG-rHuMGDF was not consistently efficacious in reducing the duration of severe thrombocytopenia. The maximum platelet counts for PEG-rHuMGDF-treated patients occurred a median of 2 weeks after the last dose of drug, suggesting that the biologic effects of this hematopoietic cytokine are delayed compared with other hematopoietic cytokines.
authors.affiliation: Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schuster
authors.forename: Roy
authors.initials: R
authors.lastname: Beveridge
authors.forename: Debra
authors.initials: D
authors.lastname: Frei-Lahr
authors.forename: Camille N
authors.initials: CN
authors.lastname: Abboud
authors.forename: Scott
authors.initials: S
authors.lastname: Cruickshank
authors.forename: Michael
authors.initials: M
authors.lastname: Macri
authors.forename: Dora
authors.initials: D
authors.lastname: Menchaca
authors.forename: Jeannine
authors.initials: J
authors.lastname: Holden
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D013926:Thrombopoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000009:adverse effects; D014182:Transplantation, Autologous; D017211:Treatment Failure
chemical_list: D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D003520:Cyclophosphamide; D013926:Thrombopoietin; D013852:Thiotepa; D016190:Carboplatin