Improved outcome with dose-dense chemotherapy.

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 antiinflammatory 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).