February 5, 2009

Dose Dense Chemotherapy: the emerging role in breast cancer treatment

More just might be better when it comes to chemotherapy for patients with early-stage breast cancer. While it’s recognized that a reduction in prescribed chemotherapy dosage and frequency can adversely impact a patient’s chance of survival, results now indicate that doses given more often may increase survival in some individuals. Although it seems logical that doses administered more often would have a greater effect, this practice has historically been limited by the risk of neutropenia (below-normal concentration of neutrophils, a type of white blood cell) and its accompanying side effects. With this threat in mind, chemotherapy administration has been limited to every three weeks. However, with successful advances in neutropenia management, dose-dense therapy is emerging as a more viable and likely more effective treatment option.

In dose-dense chemotherapy, treatment is given every two weeks rather than at the conventional three-week interval. This increased frequency is aimed to deliver the greatest amount of chemotherapy over the shortest period of time so that the cancer cells do not have time to recover or become resistant between treatment sessions. Researchers have observed positive outcomes with this higher intensity method; results show that patients with early-stage breast cancer who are treated with dose-dense chemotherapy live longer without cancer recurrence than patients treated with conventional chemotherapy.

Dose-Dense Therapy Performs in Clinical Trial

A clinical study designed to determine whether dose-dense chemotherapy could improve outcomes in women with breast cancer compared patients treated with standard chemotherapy drugs administered either every three weeks (conventional treatment) to patients treated every two weeks (dose-dense). To reduce the risk of neutropenia, all patients undergoing dose-dense therapy were also treated with Neupogen®, a white blood cell growth factor that increases production of neutrophils. Four years after completing treatment, 82 percent of patients treated with dose-dense therapy survived without cancer recurrence, compared to only 75 percent of those treated with the conventional three-week chemotherapy regimen. [1] Furthermore, patients treated with dose-dense therapy in this trial actually experienced a lower rate of severe neutropenia due to the use of Neupogen than those treated with standard chemotherapy. These results demonstrate the effectiveness of growth factors in managing side effects so that different treatment strategies may be utilized in the fight against cancer.

Controlling Neutropenia

Although the use of dose-dense chemotherapy is increasing rapidly, less than 50 percent of women with early-stage breast cancer are currently treated in this manner, despite the evidence that a dose-dense regimen reduces the risk of cancer recurrence and improves survival. Market research conducted in March 2005 with 200 medical oncologists found that only 47 percent of early-stage breast cancer patients with node-positive disease and less than 5 percent of patients with node-negative cancer were treated with dose-dense chemotherapy.

Dangers posed by neutropenia are also greater for elderly or malnourished individuals and patients undergoing multiple therapies (such as chemotherapy combined with steroids). The risks increase with each cycle of chemotherapy. Thus, neutropenia occurring in an early round of therapy is likely to return in subsequent cycles. And this complication cannot be taken lightly—one out of five cancer patients who develop febrile neutropenia experiences consequences such as infections that require intravenous antibiotic delivery in the hospital. [2] Depending on the type of cancer, the mortality rate resulting from neutropenia in cancer patients ranges from 4 to 30 percent. [3]

Promise for Future Treatment

Dose-dense therapy in the treatment of breast cancer is a breakthrough for women receiving adjuvant therapy. Due to its success, dose-dense therapies are now being studied in different types of cancers. Prior to the availability of Neupogen or Neulasta, it’s unlikely that dose-dense therapy would have been considered a feasible treatment option due to prohibitively high rates of severe neutropenia. Fortunately, these growth factors allow the safe delivery of dose-dense therapy, providing women with early breast cancer continued improvements in treatment strategies—this translates into improved long-term outcomes for the disease. As newer chemotherapy or targeted agents emerge into the clinical setting and prove to be superior to other agents, dose-dense combinations will undoubtedly evolve to incorporate these more effective agents, providing yet further advancements in the treatment of breast cancer.


1) Citron ML, Berry DA, Cirrincione C, Hudis C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of intergroup trial C9741/Cancer and Leukemia Group B trial 9741. Journal of Clinical Oncology. 2003;21:1431-9.

2) Shin DD, Godwin JE. Neutropenia [eMedicine Clinical Medicine Knowledge Base Web site]. February 7, 2002. Available at http://www.emedicine.com/med/topic1640.htm. Accessed April 20, 2005

3) Shin DD, Godwin JE. Neutropenia [eMedicine Clinical Medicine Knowledge Base Web site]. February 7, 2002. Available at http://www.emedicine.com/med/topic1640.htm. Accessed April 20, 2005

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Tags: Breast Cancer, Uncategorized