Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.
BACKGROUND
We compared docetaxel with vinorelbine for the adjuvant treatment of early breast cancer. Women with tumors that overexpressed HER2/neu were also assigned to receive concomitant treatment with trastuzumab or no such treatment.


METHODS
We randomly assigned 1010 women with axillary-node-positive or high-risk node-negative cancer to receive three cycles of docetaxel or vinorelbine, followed by (in both groups) three cycles of fluorouracil, epirubicin, and cyclophosphamide. The 232 women whose tumors had an amplified HER2/neu gene were further assigned to receive or not to receive nine weekly trastuzumab infusions. The primary end point was recurrence-free survival.


RESULTS
Recurrence-free survival at three years was better with docetaxel than with vinorelbine (91 percent vs. 86 percent; hazard ratio for recurrence or death, 0.58; 95 percent confidence interval, 0.40 to 0.85; P=0.005), but overall survival did not differ between the groups (P=0.15). Within the subgroup of patients who had HER2/neu-positive cancer, those who received trastuzumab had better three-year recurrence-free survival than those who did not receive the antibody (89 percent vs. 78 percent; hazard ratio for recurrence or death, 0.42; 95 percent confidence interval, 0.21 to 0.83; P=0.01). Docetaxel was associated with more adverse effects than was vinorelbine. Trastuzumab was not associated with decreased left ventricular ejection fraction or cardiac failure.


CONCLUSIONS
Adjuvant treatment with docetaxel, as compared with vinorelbine, improves recurrence-free survival in women with early breast cancer. A short course of trastuzumab administered concomitantly with docetaxel or vinorelbine is effective in women with breast cancer who have an amplified HER2/neu gene. (International Standard Randomised Controlled Trial number, ISRCTN76560285.).
Joensuu
Heikki
H
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Kellokumpu-Lehtinen
Pirkko-Liisa
PL
Bono
Petri
P
Alanko
Tuomo
T
Kataja
Vesa
V
Asola
Raija
R
Utriainen
Tapio
T
Kokko
Riitta
R
Hemminki
Akseli
A
Tarkkanen
Maija
M
Turpeenniemi-Hujanen
Taina
T
Jyrkkiö
Sirkku
S
Flander
Martti
M
Helle
Leena
L
Ingalsuo
Seija
S
Johansson
Kaisu
K
Jääskeläinen
Anna-Stina
AS
Pajunen
Marjo
M
Rauhala
Mervi
M
Kaleva-Kerola
Jaana
J
Salminen
Tapio
T
Leinonen
Mika
M
Elomaa
Inkeri
I
Isola
Jorma
J
D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D018734:Genes, erbB-2; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000276:immunology*; D013318:Stroke Volume / Q000187:drug effects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine