In standard adjuvant therapy for breast cancer, chemotherapy is administered every 3 weeks. However, scientists have been testing whether more frequent administration of chemotherapy would more effectively kill rapidly dividing cancer cells. In 2003, the Cancer and Leukemia Group B reported results of their randomized clinical trial of dose-dense chemotherapy, which found that a dose-dense regimen improved disease-free and overall survival in lymph node-positive early-stage breast cancer.
The Italian clinical trials group Gruppo Oncologico Nord Ovest-Mammella InterGruppo (GONO-MIG) launched a randomized clinical trial to determine whether dose-dense treatment increased overall survival and prevented relapse and whether more frequent treatment was safe or increased the level of toxic effects such as anemia, bone pain, white blood cell count, and weakness. A total of 1214 women with early-stage breast cancer were randomly assigned to receive six courses of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) either every 2 weeks (dose-dense regimen) or every 3 weeks (standard regimen). Women on the dose-dense regimen were also given filgrastim, a drug that stimulates the production of white blood cells.
Marco Venturini, M.D., of the National Cancer Research Institute in Genoa, Italy, and colleagues report that, after a median follow-up of 10.4 years, the dose-dense regimen was associated with a 13% reduced risk of death; however, this reduction was not statistically significant. Women in the dose-dense group experienced higher rates of acute toxic effects from anemia, thrombocytopenia, and bone pain. However, the authors note that these toxic effects were mild and easy to manage.
The study had some limitations. The authors designed the study to determine if the dose-dense regimen could reduce the risk of death by 32% or more. In addition, patient enrollment into the clinical trial was stopped early because of problems recruiting patients to the study.
"[O]ur results support the long-term safety of the … dose-dense chemotherapy regimen with filgrastim support as an adjuvant treatment for breast cancer," the authors write. "The dose-dense strategy was not statistically significantly associated with improved outcome, but, because of the limited statistical power of our study and the trend for an improved outcome observed, we cannot rule out the possibility of a modestly improved outcome."
"Overall, the study was thoughtfully designed, and the results are mature," write Eric P. Winer, M.D., and colleagues at the Dana-Farber Cancer Institute in Boston. Winer and colleagues write that, despite non-statistically significant results, there is still "solid evidence, in the context of other trial data, that using a dose-dense approach can decrease the risk of disease recurrence and improve overall survival."
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JNCI Journal of the National Cancer Institute