Impact of chemotherapy dose intensity on cancer patient outcomes

Abstract

Chemotherapy dose intensity represents unit dose of chemotherapy administered per unit time. Dose intensity can be increased or decreased through altering dose administered, time interval of administration, or both. Evidence supporting the importance of delivered chemotherapy dose intensity on clinical outcomes in patients with potentially curable malignancies comes from in vitro studies of cancer cell lines and abundant in vivo preclinical studies, in addition to retrospective and prospective clinical trials in both advanced and early-stage disease settings. Myelosuppression continues to represent the major dose-limiting toxicity of cancer chemotherapy, resulting in considerable morbidity and mortality along with frequent reductions in chemotherapy dose intensity, which may compromise disease control and survival. Several retrospective and prospective randomized trials have shown that reductions in the chemotherapy dose intensity established in efficacy studies may compromise long-term disease control and survival. Despite compelling data, surveys in the United States and elsewhere have reported that dose reductions and delays frequently occur in clinical practice, even in the potentially curative setting. Alternatively, an increase in dose intensity above standard may be achieved through either increasing the dose of individual agents (dose escalation) or compressing or shortening the treatment interval (dose-dense). In early studies, dose-dense schedules showed an increase in survival, whereas the benefit of dose escalation studies has been less consistent and may be accompanied by other dose-limiting toxicities. This article focuses on the rationale for delivering full chemotherapy dose intensity, the apparent reasons for failing to deliver treatment, and available strategies for sustaining full chemotherapy dose intensity when indicated. The delivery of full chemotherapy dose intensity in patients with potentially curable malignancies should be considered a quality of care indicator in clinical oncology.