Dose-dense adjuvant chemotherapy in node-positive breast cancer: docetaxel followed by epirubicin/cyclophosphamide (T/EC), or the reverse sequence (EC/T), every 2 weeks, versus docetaxel, epirubicin and cyclophosphamide (TEC) every 3 weeks. AERO B03 randomized phase II study.
BACKGROUND
Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies.


METHODS
Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC)x6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 x 4, then T 100 mg/m2 x 4 (EC-->T) or the reverse sequence (T-->EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity.


RESULTS
Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC-->T and T-->EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3-4 nail disorders, hand-foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC-->T and T-->EC, respectively.


CONCLUSIONS
Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T-->EC regimen, the incidence of grade 3-4 events makes it difficult to recommend either dose-dense regimen for further investigation.
Piedbois
P
P
Hôpital Henri-Mondor, Créteil. Electronic address: pascal.piedbois@hmn.aphp.fr.
Serin
D
D
Institut Sainte-Catherine, Avignon.
Priou
F
F
Hôpital départemental, La Roche-sur-Yon.
Laplaige
P
P
Clinique Saint-Come et Saint-Damien, Blois.
Greget
S
S
Clinique Sainte-Clotilde, Saint-Louis de la Réunion.
Angellier
E
E
Hôpital Fontenoy, Chartres.
Teissier
E
E
Clinique Plein Ciel, Mougins.
Berdah
J-F
JF
Clinique de l'Espérance, Hyères.
Fabbro
M
M
CRLCC Val d'Aurelle, Montpellier.
Valenza
B
B
Centre Hospitalier, Draguignan, France, for the European Association for Research in Oncology.
Herait
P
P
Soisy-sous-Montmorency.
Jehl
V
V
International Drug Development Institute, Brussels, Belgium.
Buyse
M
M
International Drug Development Institute, Brussels, Belgium.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide