“Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence-free survival, and nonhematologic toxic effects were more frequent in the tailored dose-dense group, according to a study appearing in the November 8 issue of JAMA.
“Dose-dense therapy, defined as delivery of chemotherapy at shorter intervals without increasing the cumulative dose, has been suggested as a means to improve efficacy of chemotherapy for early breast cancer. Dosing of most chemotherapy agents is calculated based on body surface area, which leads to large interpatient variability in toxic effects and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy.”
“Amsterdam, The Netherlands: Premenopausal women with breast cancer have a better chance of survival if they are given cycles of adjuvant chemotherapy closer together, every two weeks rather than every three weeks. Furthermore, this regimen, known as “dose-dense” adjuvant chemotherapy, does not seem to be associated with an increased risk of treatment induced early menopause.
“The findings will be presented today (Thursday) at the 10th European Breast Cancer Conference (EBCC-10) and the researchers say they are important for helping younger breast cancer patients and their doctors to make better-informed decisions about the choice of chemotherapy regimens that are given in addition to other treatments such as surgery, hormone therapy and radiotherapy.
“Dr Matteo Lambertini, MD, a medical oncologist at IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genoa, Italy , and at the Institut Jules Bordet, Brussels, Belgium, will tell the conference: ‘Our results confirm the superiority of dose-dense chemotherapy as compared to standard interval regimens in premenopausal patients at higher risk of relapse, and its use should be implemented in Europe, as it is in the United States.’ ”
“In an Italian 2×2 phase III trial reported in The Lancet, Del Mastro et al found that dose-dense adjuvant therapy with sequential epirubicin, cyclophosphamide, and paclitaxel (EC-P) with or without fluorouracil (5-FU) increased disease-free survival vs standard-interval therapy in early-stage node-positive breast cancer. No benefit of adding 5-FU to EC-P was observed.
“In this open-label trial, 2,091 patients from 81 Italian centers were randomly assigned 1:1:1:1 between April 2003 and July 2006 to receive adjuvant dose-dense chemotherapy every 2 weeks with pegfilgrastim (Neulasta) support with 5-FU plus EC-P (FEC-P, n = 500) or EC-P (n = 502) or standard-interval chemotherapy every 3 weeks with FEC-P (n = 544) or EC-P (n = 545). The primary endpoint was disease-free survival in the intention-to-treat population, with primary comparisons between every-2-week vs every-3-week schedules and FEC-P vs EC-P.
“Overall, patients had a median age of 51 to 53 years, 47% to 55% were postmenopausal, 59% to 63% had lumpectomy, 48% to 52% had T1 tumors, 57% to 64% had one to three positive nodes, 43% to 49% had grade 3 tumors, 21% to 24% were HER2-positive, 77% to 81% were estrogen or progesterone receptor–positive, and 43% to 50% had ≥ 20% Ki67-positive cells.
“The investigators concluded: ‘In patients with node-positive early breast cancer, dose-dense adjuvant chemotherapy improved disease-free survival compared with standard interval chemotherapy. Addition of fluorouracil to a sequential EC-P regimen was not associated with an improved disease-free survival outcome.’ ”