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TO THE EDITOR: Citron et al [1] have tested the hypoth-esis 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 granulo-cyte colony-stimulating factor (G-CSF) than the conven-tionally scheduled arms. An assumption is that G-CSF had no effect other than increasing neutrophil count and activ-ity 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 chemo-therapy (with scheduled G-CSF in the same dose) versus “standard ” adjuvant chemotherapy (with G-CSF as clin-ically indicated).
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Keith et al. (2004) studied this question.
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