Increased Dose Density Is Feasible: A Pilot Study of Adjuvant Epirubicin and Cyclophosphamide followed by Paclitaxel, at 10- or 11-Day Intervals with Filgrastim Support in Women with Breast Cancer

• Published in: Clinical cancer research Vol. 13; no. 1; pp. 223 - 227
• Main Authors: FORNIER, Monica N, SEIDMAN, Andrew D, HUDIS, Clifford, LAKE, Diana, D'ANDREA, Gabriella, BROMBERG, Jacqueline, ROBSON, Mark, VAN POZNAK, Catherine, PANAGEAS, Katherine S, ATIENZA, Marietta, NORTON, Larry
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-01-2007
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; breast cancer; Breast Neoplasms - drug therapy; clinical research; Cyclophosphamide - administration & dosage; Epirubicin - administration & dosage; Feasibility Studies; Female; Filgrastim; Granulocyte Colony-Stimulating Factor - administration & dosage; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Paclitaxel - administration & dosage; Pharmacology. Drug treatments; phase I-III clinical trials; Pilot Projects; Recombinant Proteins; Time Factors; Tumors; Antineoplastic agent; Human; Cytokine; Breast cancer; Malignant tumor; Density; Filgrastim; Mammary gland diseases; Alkylating agent; Granulocyte colony stimulating factor; Oxazaphosphinane derivatives; Cyclophosphamide; Nitrogen mustard; Taxane derivatives; Paclitaxel; Adult; Female; Anthracyclins; Adjuvant; Epirubicin; Woman; Antimitotic; Dose
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-1731

Purpose: Because Cancer and Leukemia Group B 9741 trial showed a benefit for every 14-day administration of chemotherapy compared
with every 21-day treatment, we hypothesized that even greater dose density would be more effective. We conducted a pilot
trial to assess the feasibility of dose-dense chemotherapy consisting of a standard regime at 10- to 11-day intervals in the
adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling logistics.
Experimental Design: Thirty-nine women with early-stage breast carcinoma were accrued from April 2004 to October 2004. Median age was 47 years
(range, 26-67 years). Patients received therapy with 100 mg/m 2 epirubicin and 600 mg/m 2 cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175 mg/m 2 paclitaxel q 10 to 11 days for four cycles, all with filgrastim support (300 μg s.c. daily) from day 2 to 24 h before the
next treatment.
Results: Thirty-five (90%) patients completed all planned therapy. The median intertreatment interval was 10 days (range, 8-28 days).
Cycles (80.7%) were delivered at no more than 10- to 11-day intervals. There were five dose reductions of 25% for grade 3
nonhematologic toxicity in five patients. Six (16%) patients developed febrile neutropenia defined as temperature >38°C with
absolute neutrophil count <1,000/μL. All febrile neutropenia was during therapy with EC. Other grade 3 toxicities included
bone pain, hand and foot syndrome, neuropathy, mucositis, nausea, and vomiting.
Conclusions: Therapy with EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day intervals is feasible. The ∼30% reduction
in intertreatment interval compared with every 14-day treatment could increase the efficacy of adjuvant chemotherapy.