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Annals of Oncology Advance Access published online on June 2, 2005
Annals of Oncology, doi:10.1093/annonc/mdi264
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© 2005 European Society for Medical Oncology
Received December 17, 2004
Revised March 17, 2005
Accepted March 23, 2005

Review

Chemotherapy dose intensity in non-Hodgkin's lymphoma: is dose intensity an emerging paradigm for better outcomes?

S. A. Gregory 1* and L. Trümper 2

1 Rush University Medical Center, Section of Hematology and Stem Cell Transplantation, Chicago, IL, USA
2 Georg August University, Department of Hematology and Oncology, Göttengen, Germany

* To whom correspondence should be addressed.
S. A. Gregory, E-mail: stephanie_gregory{at}rush.edu


  Abstract

Background: Higher chemotherapy dose intensity has been studied as a way of improving the clinical outcomes in various malignancies, including non-Hodgkin's lymphoma (NHL).

Methods: We reviewed clinical trials that have studied the relation between dose and response in cancer chemotherapy, the theory behind dose-intense chemotherapy, and the clinical results with dose-escalated and dose-dense therapy in aggressive NHL.

Results: Myeloablative high-dose chemotherapy with stem cell transplantation produces higher 5-year survival rates than standard salvage chemotherapy in relapsed aggressive lymphoma, but its role as initial therapy is not yet clear. Nonmyeloablative dose-escalated chemotherapy is feasible with granulocyte colony-stimulating factor (G-CSF) support, but this approach does not improve outcomes. Dose-dense (14-day) CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with G-CSF support produces better results than 21-day CHOP in patients with previously untreated aggressive lymphoma, without additional toxicity. The addition of etoposide to dose-dense CHOP may provide further benefits in younger patients. The addition of rituximab to G-CSF-supported dose-dense CHOP is feasible. Preliminary data suggest the feasibility of dose-dense chemotherapy for NHL with the once-per-cycle G-CSF, pegfilgrastim.

Conclusion: Dose-dense chemotherapy with G-CSF support produced better clinical outcomes in both younger and older patients. Phase 3 trials of dose-dense CHOP plus rituximab with CSF support are warranted.

Keywords: chemotherapy; colony-stimulating factor; filgrastim; neutropenia; non-Hodgkin's lymphoma; pegfilgrastim.
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