Dose dense adjuvant chemotherapy in breast cancer – pro

Since 1998, the standard of adjuvant care for patients with node-positive breast cancer in the United States and other parts of the world has been treatment with doxorubicin and cyclophosphamide followed by the taxane paclitaxel.  This regimen was first administered on a schedule of once every three weeks and then, more recently, once every two weeks, after a comparative trial demonstrated improved efficacy (a 7 percent absolute improvement in disease-free survival and a 2 percent improvement in overall survival at three years) with the schedule involving more frequent administration (referred to as dose-dense therapy).

The issues of toxicity are well worked out in both adjuvant and metastatic setting. In metastatic setting, dose dense chemo yilds higher response rates. Weekly administration of the drug paclitaxel (Taxol®) to patients with breast cancer that had spread to other parts of the body resulted in a higher response rate and a longer delay until patients’ disease progressed, compared with conventional administration of the drug every three weeks. A Phase III trial conducted in Germany studied 1284 patients under the age of 65 who had at least four lymph nodes containing metastatic cancer. Patients were assigned to receive either dose-dense chemotherapy or conventional treatment. At five years the relapse-free survival was 70 percent in the dose-dense arm, compared with 62 percent in the conventional-dose arm. Patients did seem to have a lower quality of life with the dose-dense method of treatment but recovered after a few months.

In terms of effectiveness, there is only one study, as cited above. NCCN lists dose-dense therapy. Although this one study has given promising results, it’s still too early to say if dose-dense chemotherapy is better than standard chemotherapy. However, there is expert consensus that it is not worse and not more toxic. It is thus equivalent to q 3 weeks non-dense therapy and should not be considered experimental or not med. necessary. The drugs themselves are FDA approved: “TAXOL is indicated for the adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy.”

Citron ML 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. J Clin Oncol 2003;21(7):1-9.

Jackisch C, Von Minckwitz G, Raab G, et al. Primary endpoint analysis of the GEPARDUO study — preoperative chemotherapy comparing dose-dense versus sequential Adriamycin/docetaxel combination in operable breast cancer. Program and abstracts of the 25th Annual San Antonio Breast Cancer Symposium; December 11-14, 2002; San Antonio, Texas. Abstract 152.

Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C.Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840.J Clin Oncol. 2008 Apr 1;26(10):1642-9. Comment in: J Clin Oncol. 2008 Apr 1;26(10):1585-7.

nccn, breast cancer, BINVK-7, 2017

H. Joensuu et al, Adjuvant treatments for triple-negative breast cancers Ann Oncol (2012) 23 (suppl 6): vi40-vi45.

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