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Improved Outcome With Dose-Dense Chemotherapy

Windsor Regional Cancer Centre, Windsor, Ontario, Canada
Division of Hematology/Oncology, Michigan State University, East Lansing, MI

To the Editor:

Citron et al [1] have tested the hypothesis that outcome is improved with increased dose density of chemotherapy. Although it is not stated, it is likely that the dose-dense arms received considerably more granulocyte colony-stimulating factor (G-CSF) than the conventionally scheduled arms. An assumption is that G-CSF had no effect other than increasing neutrophil count and activity against infection. However, G-CSF has been found to stimulate other potentially antitumor immune functions, including chemotaxis [2], adhesion [3], pre–B cells [4], and T helper cell type 2–inducing dendritic cells [5]. G-CSF can also have an anti-inflammatory effect [6]. Inflammation is thought to play an important role in cancer, and an anti-inflammatory approach to cancer treatment has been proposed [7]. Is the improved outcome due to increased dose density of chemotherapy, to increased G-CSF use, or both? To answer that question, an appropriate trial would be "dose-dense" adjuvant chemotherapy (with scheduled G-CSF) versus "standard" adjuvant chemotherapy (with scheduled G-CSF in the same dose) versus "standard" adjuvant chemotherapy (with G-CSF as clinically indicated).

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Citron ML, Berry DA, Cirrincione C, et al: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1431-1439, 2003[Abstract/Free Full Text]

2. Wang JM, Chen ZG, Colella S, et al: Chemotactic activity of recombinant human granulocyte colony-stimulating factor. Blood 72:1456-1460, 1988[Abstract/Free Full Text]

3. Okada Y, Kawagishi M, Kusaka M: Effect of recombinant human granulocyte colony-stimulating factor on human neutrophil adherence in vitro. Experientia 46:1050-1053, 1990[CrossRef][Medline]

4. Woodward TA, McNiece IK, Witte PL, et al: Further studies on growth factor production by the TC-1 stromal cell line: Pre-B stimulating activity. Blood 75:2130-2136, 1990[Abstract/Free Full Text]

5. Stull DM: Colony-stimulating factors: Beyond the effects on hematopoiesis. Am J Health Syst Pharm 59:12-20, 2002 (suppl 2)

6. Hartung T: Anti-inflammatory aspects of Filgrastim and impact on IL-2 release. J Hematother Stem Cell Res 8:21-22, 1999 (suppl 1)

7. Coussens LM, Werb Z: Inflammation and cancer. Nature 420:860-867, 2002[CrossRef][Medline]

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• Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741
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Related Reply

• In Reply:
  Marc L. Citron, Donald A. Berry, Constance Cirrincione, Clifford Hudis, Larry Norton, Eric P. Winer, William J. Gradishar, Nancy E. Davidson, Silvana Martino, Robert Livingston, James N. Ingle, John Carpenter, David Hurd, James F. Holland, Barbara Smith, Carolyn I. Sartor, Eleanor H. Leung, Jeffrey Abrams, Richard L Schilsky, and Hyman B. Muss
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