ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03630.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Adjuvant chemotherapy improves the disease‐free and overall survival of patients with resectable, early‐stage breast cancer. However, the effect is modest, and we need means of increasing its impact. Retrospective and prospective studies on the effects of increased drug dosage have demonstrated that within some dose ranges, increasing the dose intensity (total drug dose divided by total treatment time) improves the outcome of treatment. Dose escalation to higher levels, sufficient to require growth factor and autologous stem cell support, is the subject of ongoing randomized study. Because there are both theoretical and practical limits on the potential effectiveness of single‐cycle, high‐dose chemotherapy, researchers are developing alternative means of increasing the effect of chemotherapy. One theoretically advantageous approach, predicted to be superior by kinetic models, is “dose‐dense” chemotherapy administration. This approach consists of multiple cycles of escalated‐dose chemotherapy administered at very short intervals. When administering presumed non‐cross‐resistant regimens or agents with overlapping toxicity, clinicians can increase dose density by using the sequential treatment plan. Furthermore, this plan can also facilitate the addition

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03631.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Increasing evidence supports the hypothesis that “dose” is critical to the clinical outcomes of cytotoxic chemotherapy for patients with breast cancer. Clinical trials continue to investigate whether higher doses of chemotherapy lead to proportionate improvements in the outcomes of patients. Delivery of dose‐intensive chemotherapy has been facilitated by technological advancements in supportive care. Improved antiemetics have led to increased patient tolerance of the most acute symptoms of aggressive chemotherapeutic dosing. Chemotherapy‐induced myelosuppression may be minimized in a lineage‐specific manner by appropriate use of hematopoietic cytokines such as filgrastim (granulocyte colony‐stimulating factor), sargramostim (granulocyte‐macrophage colony‐stimulating factor), and/or epoetin alfa (erythropoietin). However, cumulative myelotoxicity occurs with dose‐intensive chemotherapy over multiple cycles despite adjunctive cytokine support. Additionally, no cytokine has yet been demonstrated to support platelet production to any clinically significant degree although several regulators of platelet production (such as thrombopoietin, IL‐6, and IL‐11) are in clinical trials. Many cytokines can induce the mobilization of hematopoietic progenitor and stem cells from the bone marrow into the circulating blood pool, where these cells may be harvested. Clinical use of these cytokine‐mobilized peripheral blood progenitor cells (also known as PBPCs or, commonly, as blood stem cells) has documented the effectiveness of these cells to reconstitute multilineage blood production following very high‐dose chemotherapy. The ease with which PBPCs can be collected and their reproducible clinical effectiveness to support patients through intensive treatment protocols have led to a virtual elimination of bone marrow as the source of cellular support for myeloablative chemotherapy in many transplant centers. Novel investigative approaches are also possible with PBPCs. In this review, the historical background of PBPCs is summarized, and the potential benefits (including economic advantages) of PBPCs to support dose‐intensive chemotherapy for treating breast cancer are discussed. While dose intensification of breast cancer chemotherapy to the degree requiring PBPC support remains controversial and, in most centers, investigational, there is no doubt that PBPCs are an effective adjunct to the hematopoietic support of patients undergoing transplant‐level cytotoxic treatments. Further study will undoubtedly lead to increased use of PBPCs in novel treatments for patients with breast

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03632.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The recent observation that mobilized peripheral blood progenitor cells (PBPCs) can be used as a source of hematopoietic support has had a major effect on the cost and morbidity associated with bone marrow transplantation in patients with breast cancer. The pharmacoeconomic impact of this new technology is especially evident when secondary costs are analyzed. We see a reduction in hospital stay, decreased use of resources such as platelet transfusions and antibiotics, and long‐term quality life‐years gained for those patients benefiting from this therapy. Experienced transplant centers have found that the direct cost of high‐dose chemotherapy using filgrastim and PBPC support is reduced as much as 50% to the patient or their insurance company. Pharmacists will play a key role in optimizing the benefits of PBPC transplantation, particularly because this therapy is moving to the outpatient arena. This article will review the pharmacoeconomic impact of PBPC transplantation primarily in terms of secondary cost measures and quality of life and discuss the limited direct cost data available and the impact of this therapy on pharmacy pra

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03633.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Peripheral blood has replaced bone marrow as a source of hematopoietic stem cells for autologous rescue after high‐dose chemotherapy. Patients who receive peripheral blood stem cell (PBSC) transplants experience rapid and sustained hematopoietic reconstitution. As a result, transplant‐related mortality is now less than 5% at many centers, and the cost of high‐dose chemotherapy has decreased considerably. However, the relapse rate continues to be unacceptably high, and the collection of hematopoietic stem cells from peripheral blood is inconvenient, time consuming, and expensive. This article discusses the current status of novel technologies such as positive selection of hematopoietic stem cells, ex vivo expansion of hematopoietic progenitor cells, allogeneic PBSC transplants, and umbilical cord blood transplants. Several companies are actively developing devices that positively select hematopoietic stem cells. Because positive selection reduces the volume of infused cells, patients experience fewer adverse effects related to dimethylsulfoxide (DMSO) or lysed cells. These devices may also serve as an ex vivo method to remove (“purge”) residual tumor cells. Positively selected hematopoietic stem cells may be expanded ex vivo to produce a large number of a specific population of hematopoietic cells. By adding cytokines that stimulate and activate lymphocytes, natural killer cells, and other immune effector cells, investigators could expand the number of immune effector cells with antitumor activity and then infuse them into patients as a form of adoptive immunotherapy. Finally, peripheral blood and umbilical cord blood are promising new sources of hematopoietic stem cells for allogeneic tr

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03634.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY