Experimental and clinical observations of the proliferation of @entity5 cells and their responses to cytotoxic drugs already have had an impact on the design of anticancer therapies and it is possible that further understanding of the natural history of @entity5 will enable better treatments to be developed. This review addresses several approaches to improving the prognosis for @entity1 with @entity0 in which our understanding of @entity5 dynamics plays an important role. Increasing dose intensity can be achieved by dose escalation (increasing the amount of drug) or increasing dose density (reducing the time between treatments). The Gompertzian model of @entity5 growth, which is concordant with many experimental and clinical observations, can offer an explanation why, although dose escalation improves the number of clinical responses, cure is still uncommon. In the Gompertzian model, smaller @entity5 grow faster, so @entity5 regrowth between treatment cycles is more rapid when cell kill is greatest. Reducing the time available for @entity5 regrowth (increasing dose density), which is now possible through the use of colony-stimulating factors to hasten hematopoietic recovery, may have a greater impact on clinical outcome than dose escalation. Sequential schedules allow optimal doses to be used in dose-dense cycles. Several cycles of the optimal dose of agent A, followed by several cycles of the optimal dose of agent B, may be more effective than the simultaneous combination of suboptimal doses of A and B. In this context, agents A and B may be single agents or established combinations. This tactic allows new agents, such as the taxoids, to be used in conjunction with established therapies, such as @entity632 plus @entity786 , at optimal doses in dose-intensive regimens. Although such regimens may maximize cytoreduction, this may not be sufficient to improve significantly the long-term outcome for @entity1 with @entity0 . A recent trial using high-dose consolidation chemotherapy with autologous bone marrow support has thrown doubt on the assertion, implicit in Gompertzian cytodynamics, that optimal cytotoxic therapy can kill all @entity5 cells. The results of this trial suggest that a consistent number of @entity5 cells remain whether high-dose chemotherapy with autologous bone marrow support is used in @entity1 in complete pathologic remission or in @entity1 with overt relapse. If there is a lower limit to cytoreduction, other approaches must be developed to control or prevent the regrowth of @entity41 cells. This will require a better understanding of the molecular biology of @entity0 and the ability to predict and assess the sensitivity of individual @entity1 's @entity5 to particular therapies. Factors such as @entity1722 overexpression are already being linked to sensitivity to particular agents and the products of oncogenes such as @entity1722 may be targeted by biologic therapies such as monoclonal antibodies. Furthering our understanding of the biology and behavior of @entity5 cells may lead to significant improvements in the long-term prognosis for @entity1 with early and @entity0 .

Evolving concepts in the systemic drug therapy of XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'advanced breast cancer'] @entity41 :: ('MESH:D018365', 'Disease') :: ['residual tumor'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'tumors'] @entity786 :: ('MESH:D003520', 'Chemical') :: ['cyclophosphamide'] @entity1722 :: ('2064', 'Gene') :: ['HER2']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer']
