Phase II study of feasibility of dose-dense FEC followed by alternating weekly taxanes in high-risk, four or more node-positive breast cancer.
OBJECTIVE
To develop a potentially superior adjuvant chemotherapy regimen, we conducted a pilot study of dose-dense 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by weekly alternating taxanes. The primary objective was to determine the feasibility of the regimen; the secondary objective was to estimate the disease-free and overall survival.


METHODS
Patients with >/=4 node-positive breast cancer were studied. Treatment consisted of FEC at 500/100/500 mg/m(2), respectively, x6 at two-week intervals with granulocyte colony-stimulating factor, followed by weekly paclitaxel (80 mg/m(2)) alternating with docetaxel (35 mg/m(2)) x18.


RESULTS
Between November 2001 and January 2003, 44 patients were enrolled. Median age was 46 years (range, 26-63 years), median number of positive nodes was 9 (range, 4-32), and median tumor size was 2.5 cm (range, 0.6-11.0 cm). Because of unexpected toxicities, the study was stopped when 17 (39%) had fully completed all of the planned treatment. Two of 17 (12%) developed grade 4 pericardial/grade 3 bilateral pleural effusions at treatment completion; both required pericardial window. The remaining patients were treated with taxanes using one of several standard dose and schedule combinations. Furthermore, 4 of 44 (9%) developed pneumonitis attributed to the FEC regimen. Hospital admissions were required for 12 of 44 (27%); 3 of 44 (7%) required blood transfusions. There were no treatment related deaths. Median disease-free and overall survival will not be estimatable because of early closure of study.


CONCLUSIONS
FEC x6 at 2-week intervals followed by 18 weeks of alternating taxanes is not feasible at the doses tested. Other strategies are needed to improve adjuvant systemic chemotherapy.
Dang
Chau T
CT
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. dangc@mskcc.org
D'Andrea
Gabriella M
GM
Moynahan
Mary E
ME
Dickler
Maura N
MN
Seidman
Andrew D
AD
Fornier
Monica
M
Robson
Mark E
ME
Theodoulou
Maria
M
Lake
Diana
D
Currie
Violante E
VE
Hurria
Arti
A
Panageas
Katherine S
KS
Norton
Larry
L
Hudis
Clifford A
CA
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D012307:Risk Factors; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil