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

Craig Moskowitz, P. A. Hamlin, J. Gabrilove, J. R. Bertino, C. S. Portlock, D. J. Straus, A. N. Gencarelli, Stephen D Nimer, A. D. Zelenetz

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Introduction: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)1842-1850
Number of pages9
JournalAnnals of Oncology
Volume18
Issue number11
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

Non-Hodgkin's Lymphoma
Placebos
Drug Therapy
Survival
Blood Platelets
Thrombocytopenia
Stem Cells
Platelet Transfusion
Disease-Free Survival
polyethylene glycol-recombinant human megakaryocyte growth and development factor
Outcome Assessment (Health Care)
Safety

Keywords

  • Dose-intensity
  • ICE chemotherapy
  • Non-Hodgkin's lymphoma
  • Refractory
  • Relapsed
  • Transplantation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Moskowitz, Craig; Hamlin, P. A.; Gabrilove, J.; Bertino, J. R.; Portlock, C. S.; Straus, D. J.; Gencarelli, A. N.; Nimer, Stephen D; Zelenetz, A. D.

In: Annals of Oncology, Vol. 18, No. 11, 01.11.2007, p. 1842-1850.

Research output: Contribution to journalArticle

Moskowitz, Craig ; Hamlin, P. A. ; Gabrilove, J. ; Bertino, J. R. ; Portlock, C. S. ; Straus, D. J. ; Gencarelli, A. N. ; Nimer, Stephen D ; Zelenetz, A. D. / 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. In: Annals of Oncology. 2007 ; Vol. 18, No. 11. pp. 1842-1850.
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abstract = "Introduction: 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). Conclusion: 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.",
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T1 - 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

AU - Moskowitz, Craig

AU - Hamlin, P. A.

AU - Gabrilove, J.

AU - Bertino, J. R.

AU - Portlock, C. S.

AU - Straus, D. J.

AU - Gencarelli, A. N.

AU - Nimer, Stephen D

AU - Zelenetz, A. D.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Introduction: 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). Conclusion: 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.

AB - Introduction: 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). Conclusion: 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.

KW - Dose-intensity

KW - ICE chemotherapy

KW - Non-Hodgkin's lymphoma

KW - Refractory

KW - Relapsed

KW - Transplantation

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DO - 10.1093/annonc/mdm341

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