Dose and outcome: the hurdle of neutropenia (Review)

The development of chemotherapy in the early 1970s resulted in the availability of curative therapeutic strategies for hematological malignancies and several types of solid tumors. It is evident that drugs should be used at their optimal dose and schedule, and drug combinations should be given at consistent intervals. According to the mathematical models that suggested the direct dose-response relationship in the improvement of outcomes in cancer chemotherapy, the dose intensity and, more recently, the dose-dense approach was considered one of the most important tools in conventional chemotherapy. Anticancer drugs are often associated with myelotoxicity, and reducing the dose or increasing the time interval between each cycle of treatment is a frequent empiric approach. Unfortunately, a dose reduction of >or=20% causes a loss of 50% in the cure rate, particularly in chemosensitive tumors. To accelerate bone marrow recovery and prevent the onset of severe myelosuppression and its complications, the standard use of granulocyte colony-stimulating factors (G-CSF), such as filgrastim and the long-acting pegfilgrastim, is recommended. The aim of this review is to analyze how dose intensification concepts and dose-dense regimens are able to increase the cure rate of chemosensitive solid tumors and lymphomas.