Increased dose-density (DD) Is feasible: A pilot study of epirubicin and cyclophosphamide (EC) followed by paclitaxel (T), at 10–11 day interval with filgrastim support, for women with early breast carcinoma (BC)

Abstract

616 Background: Q 14 day chemotherapy (CRx) was superior to q 21 day treatment in CALGB 97–41. (Citron et al, J Clin Oncol 2003 Apr 15;21(8):1431–9) Hence we hypothesized that even greater DD (q 10–11) could be more effective. This pilot trial assessed the feasibility of neoadjuvant/adjuvant DD CRx consisting of EC x 4 followed by T x 4 at 10–11 day intervals. A 2 day window was allowed for logistical reasons. Methods: 39 women with early stage BC were accrued from April 2004 to October 2004. Median age was 47 (range 26–67). Patients (pts) received therapy with EC (E 100 mg/m2 and C 600 mg/m2) q 10–11 days for 4 cycles followed by T 175 mg/m2 q 10–11 days for 4 cycles, all with filgrastim support from day 2 to 24 hours before the next treatment. Results: As of 12/1/04 31 pts have completed all planned therapy and 38 pts have completed EC. 4 pts are still receiving T. 4 pts did not complete all planned therapy: 1 pt withdrew consent after EC # 1 for non-medical reasons; 2 pts switched to docetaxel after T #3 due to allergic reactions; 1 pt withdrew after T #3 because of grade 3 neuropathy. The median inter-treatment interval was 10 days (range 8–28). 80.3% of pts were treated at 10–11 day intervals or less. One patient had one 8 day interval for T #2 due to scheduling logistics. One patient had one 28 day interval because of logistical delays associated with a venous access device placement. There were 5 dose-reductions of 25% for grade 3 non-hematological toxicity in 5 pts. 6 pts (16%) developed febrile neutropenia (FN) defined as temperature ≥ 38°C with ANC < 1000/μL; 1 pt developed FN twice (7 events). All FN was during EC. There were 9 hospitalizations: 7 FN, 1 pharyngitis and afebrile neutropenia, 1 tissue expander infection. Other grade 3 toxicities include: 3 bone pain/myalgia, 2 hand and foot syndrome, 2 neuropathy, 1 mucositis, 1 nausea and vomiting. Conclusions: EC followed by T at 10–11 days is feasible, without excessive toxicity. The nearly 30% reduction in inter-treatment interval compared to 14 day treatment could increase the efficacy of adjuvant chemotherapy and should be tested in a prospective randomized trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Pfizer Amgen, Pfizer Amgen, Pfizer