Annals of Oncology Advance Access originally published online on September 14, 2007
Annals of Oncology 2007 18(11):1842-1850; doi:10.1093/annonc/mdm341
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© 2007 European Society for Medical Oncology
hematologic malignancies |
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
1 Hematology Service
2 Lymphoma Service, Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
3 Current address: The James F. Holland Professor of Medicine, The Mount Sinai School of Medicine, The Department of Medicine, Division of Hematology/Oncology, New York, NY
4 Current address: Cancer Institute of New Jersey, Robert wood Johnson School of Medicine, New Brunswick, NJ, USA
* Correspondence to: Dr Craig Moskowitz, 1275 York Ave., Box 350, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Tel: +1-212-639-2696; Fax: +1-646-422-2164; E-mail: moskowic{at}mskcc.org
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.
Key words: dose-intensity, ICE chemotherapy, non-Hodgkin's lymphoma, refractory, relapsed, transplantation
These authors contributed equally to writing the manuscript and analyzing the data. Received for publication December 27, 2006. Revision received April 19, 2007. Accepted for publication May 31, 2007.
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