Pant et al risk of relapse with FEC→D compared with FEC alone (p = 0.04). Similar beneﬁts were not observed in women with more than 3 positive lymph nodes. Interestingly, the beneﬁt in DFS was more apparent in women age 50 years or older (p = 0.001) than in younger women (p = 0.65). The addition of docetaxel was associated with a higher rate of febrile neutropenia, but the overall incidence of grade 3 or 4 neutropenia in cycles 4–6 was higher in the FEC group (20.2% vs 10.9 %) The use of growth factors was signiﬁcantly increased in patients receiving 6 cycles of FEC (p 0.001) Treatment with FEC-D was associated with signiﬁcantly fewer cardiac events. Safety data from ongoing studies have been reported. The data on efﬁcacy are awaited. The BCIRG 005 study randomized 3298 patients with node-positive breast cancer to either 6 cycles of docetaxel (75 g/m2), doxorubicin, and cyclo- phosphamide (TAC) or 4 cycles of doxorubicin and cyclo- phosphamide, followed by docetaxel (T) (100 mg/m2). Both regimes were administered every 3 weeks (Eiermann et al 2005). Patients were given prophylactic ciproﬂoxacin and G-CSF was administered at the time of febrile neutropenia. There was an increased incidence of febrile neutropenia in the TAC group (17.9% vs 8.5%), and more neurotoxicities and myalgias in the AC followed by T arm. In the phase III PACS 04 trial, patients were randomized to receive 6 cycles of FEC 100 or 6 cycles of epirubicin and docetaxel (75 mg/m2) (ET). The patients in the ET arm had an increased incidence of febrile neutropenia (31% vs 10.7%) while there was a signiﬁcant decline in the left ven- tricular ejection fraction seen in the FEC arm (Spielmann et al 2006). A phase II trial (Piedbois et al 2005) evaluated grade 4 toxicities of 6 cycles of docetaxel (75 mg/m2), epirubicin (75 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks (control group) or 4 cycles of epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2 ) every 2 weeks (arm A) or 4 cycles of docetaxel followed by 4 cycles of epirubicin and cyclo- phosphamide (arm B), in 100 patients with node-positive breast cancer. Prophylactic pegﬁlgastrim was administered. Sixty-one patients were evaluated for toxicity. Grade 3/4 toxicities of the control arm compared with arm A or arm B included neutropenia (38% vs 35% vs 33%), hand foot syndrome (0% vs 25% vs 33%), neurotoxicity (0% vs 15% vs 6%), and nausea (0% vs 155 vs 6%) respectively. The incidence of febrile neutropenia was highest in the control group (14% vs 5% vs 0%). These regimens remain to be tested in phase III trials. 422 An ongoing Italian study randomized patients to receive either 4 cycles of EC (epirubicin 120 mg/m2 and cyclophos- phamide 600 mg/m2) Q21 days or 4 cycles of docetaxel (100 mg/m2) followed by 4 cycles of EC. Initial data on toxicity revealed a higher rate of grade 4 neutropenia and febrile neutropenia in the docetaxel arm with an increased incidence of grade 3/4 nausea/vomiting in the EC arm (Valeria et al 2001). In summary, studies in node-positive breast cancer with docetaxel given concurrently or sequentially with anthra- cyclines improved disease-free survival. This beneﬁt was most evident in patients with fewer than 3 positive nodes. Prophylactic use of growth factors should be considered in patients receiving docetaxel in combination with other myelosuppressive chemotherapy. Docetaxel in studies including both node-negative and node-positive breast cancer A number of important studies addressing docetaxel in the adjuvant setting have included both node-negative and node- positive patients. The Eastern Cooperative Oncology Group (ECOG) trial E2197 randomized 2952 women to 4 cycles of AT (adriamycin 60 mg/m2, docetaxel 60 mg/m2) or 4 cycles of AC (adriamycin 60 mg/m2, cyclophosphamide 600 mg/m2), administered every 3 weeks for 4 cycles. Thirty-ﬁve percent of the patients were lymph node-positive. After a median follow-up of 53 months, DFS was identical (87%) in both groups of patients. The incidence of febrile neutropenia was higher with AT (19%) than with AC (6%). There were 3 treatment related-deaths in the AT arm. The difference in efﬁcacy could be attributed to the lower dose of docetaxel and fewer node-positive patients in this ECOG trial. Jones et al (2006) randomized 1601 patients with stage I to III operable invasive breast cancer to 4 cycles of AC (60 mg/m2 and 600 mg/m2 respectively) or TC (75 mg/m2 and 600 mg/m2 respectively), administered every 3 weeks in the adjuvant setting. The 5-year DFS rate was superior for TC than AC (86% vs 80%, p = 0.15). The patients in the AC arm experienced more grade 1 to 4 nausea and vomiting (p 0.01), whereas more fever and neutropenia was observed with TC (5%) vs AC (2.5%, p = 0.07). In the AC group, 1 patient died form congestive heart failure and 1 patient in the TC group died of sepsis and neutropenia. In a subgroup analysis, both node-negative (TC = 239, AC = 248) and node-positive (TC = 267, AC = 262) patients seemed to favor the TC arm. The HR for node-negative patients was 0.73 and for the node-positive patients was 0.67, but this Therapeutics and Clinical Risk Management 2008:4(2)