Short-term administration of granulocyte-macrophage colony stimulating factor decreases hematopoietic toxicity of cytostatic drugs

Background. Administration of granulocyte-macrophage colony stimulating factor (GM-CSF) is followed by a rapid increase in the proliferative activity of the hematopoietic precursors. Within 72 hours after its suspension, however, establishment of a negative feedback results in a reduction of the proliferative activity of the hyperplastic marrow to values below the baseline, suggesting refractoriness of hematopoietic progenitors to the action of cell-cycle-specific cytostatic agents. Methods. The hypothesis that short treatment with GM-CSF before chemotherapy could reduce the hematopoietic toxicity of cytostatics was investigated by administering GM- CSF glycosylate (Sandoz, Basel, Switzerland/Schering-Plough, Kenilworth, NJ) subcutaneously with a 5.5 μg/kg protein dosage per day from day -6-day -4 before each course of adjuvant chemotherapy (cyclophosphamide, epirubicin, 5- fluorouracil/cyclophosphamide, methotrexate, 5-fluorouracil alternate) in patients with node-positive breast cancer. Twelve patients were randomized to receive GM-CSF before chemotherapy or only at chemotherapy. The hematologic picture and dose intensity of chemotherapy were compared in the two groups of patients. Results. In the group of patients receiving chemotherapy only, 22% of the cycles had to be postponed because of leukopenia, with a consequent reduction of the dose intensity, whereas in the GM-CSF group, the neutrophil counts remained at significantly (P <0.001) higher levels, and there were no delays in chemotherapy administration. No substantial systemic toxicity was associated with this brief GM-CSF schedule. Moreover, GM-CSF treatment did not result in delayed depletion of the hematopoietic pool. Conclusions. Short treatment with GM-CSF can enable the dose intensity of conventional protocols of proven efficacy to be increased.