title: Maintaining the dose intensity of ICE chemotherapy with a thrombopoietic agent, PEG-rHuMGDF, may confer a survival advantage in relapsed and refractory aggressive non-Hodgkin lymphoma.
abstract: BACKGROUND
  HDT/ASCT is standard for relapsed and refractory DLCL patients responding to second-line chemotherapy. We incorporated a thrombopoietic agent into the ICE chemotherapy program to potentially: decrease platelet associated toxicities, augment stem cell collection and maintain dose intensity.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled phase I/II trial examines PEG-rHuMGDF versus placebo with ICE chemotherapy. Phase I compared three cohorts and defined a clinically effective dose (CED). Phase II evaluated the CED versus placebo. Outcome measures included safety, hematological end-points, stem cell collection and the impact of dose-intensity on outcome.
  
  
  RESULTS
  Forty-one patients with primary refractory (16) or relapsed DLCL (25) were treated; Response rates for evaluable patients are: 75% (12/16) for placebo and 82% (18/22) for PEG-rHuMGDF. PEG-rHuMGDF treated patients had significantly less grade IV thrombocytopenia, higher median platelet nadirs, and less platelet transfusion per cycle. ICE dose intensity was improved with PEG-rHuMGDF versus placebo: 75 versus 42% (P = 0.008). At 8.5 years median follow-up, overall and event-free survival are 47 and 31%, respectively. Patients treated on PEG-rHuMGDF versus placebo had improved survival (59 versus 31%, P = 0.06).
  
  
  CONCLUSIONS
  PEG-rHuMGDF ameliorated thrombocytopenia, improved platelet recovery, and maintained ICE dose intensity. Potential survival advantages conferred by maintaining dose intensity require validation with newer thrombopoietic agents.
authors.affiliation: Hematology Service, New York, NY, USA. moskowic@mskcc.org
authors.forename: C H
authors.initials: CH
authors.lastname: Moskowitz
authors.forename: P A
authors.initials: PA
authors.lastname: Hamlin
authors.forename: J
authors.initials: J
authors.lastname: Gabrilove
authors.forename: J R
authors.initials: JR
authors.lastname: Bertino
authors.forename: C S
authors.initials: CS
authors.lastname: Portlock
authors.forename: D J
authors.initials: DJ
authors.lastname: Straus
authors.forename: A N
authors.initials: AN
authors.lastname: Gencarelli
authors.forename: S D
authors.initials: SD
authors.lastname: Nimer
authors.forename: A D
authors.initials: AD
authors.lastname: Zelenetz
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D017567:Karnofsky Performance Status; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011336:Probability; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage; D012016:Reference Values; D016019:Survival Analysis; D013926:Thrombopoietin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D003520:Cyclophosphamide; D013926:Thrombopoietin; D000069585:Filgrastim; D007069:Ifosfamide