Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial.
BACKGROUND
Standard adjuvant chemotherapy regimens for patients with moderate-to-high-risk early breast cancer typically contain a taxane, an anthracycline, and cyclophosphamide. We aimed to investigate whether integration of capecitabine into such a regimen enhances outcome.


METHODS
In this open-label trial, we randomly assigned (centrally by computer; stratified by node status, HER2 status, and centre) 1500 women with axillary node-positive or high-risk node-negative breast cancer to either three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753), or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The primary endpoint was recurrence-free survival. A planned interim analysis was done after 3 years' median follow-up. Efficacy analyses were by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT00114816.


RESULTS
Two patients in each group were excluded from efficacy analyses because of withdrawal of consent or distant metastases. After a median follow-up of 35 months (IQR 25.5-43.6), recurrence-free survival at 3 years was better with the capecitabine regimen than with control (93%vs 89%; hazard ratio 0.66, 95% CI 0.47-0.94; p=0.020). The capecitabine regimen was associated with more cases of grade 3 or 4 diarrhoea (46/740 [6%] vs 25/741 [3%]) and hand-foot syndrome (83/741 [11%] vs 2/741 [<1%]) and the control regimen with more occurrences of grade 3 or 4 neutropenia (368/375 [98%] vs 325/378 [86%]) and febrile neutropenia (65/741 [9%] vs 33/742 [4%]). More patients discontinued planned treatment in the capecitabine group than in the control group (178/744 [24%] vs 23/741 [3%]). Four patients in the capecitabine group and two in the control group died from potentially treatment-related causes.


CONCLUSIONS
The capecitabine-containing chemotherapy regimen reduced breast cancer recurrence compared with a control schedule of standard agents. Capecitabine administration was frequently discontinued because of adverse effects.


BACKGROUND
Roche, Sanofi-Aventis, AstraZeneca, Cancer Society of Finland.
Joensuu
Heikki
H
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. heikki.joensuu@hus.fi
Kellokumpu-Lehtinen
Pirkko-Liisa
PL
Huovinen
Riikka
R
Jukkola-Vuorinen
Arja
A
Tanner
Minna
M
Asola
Raija
R
Kokko
Riitta
R
Ahlgren
Johan
J
Auvinen
Päivi
P
Hemminki
Akseli
A
Paija
Outi
O
Helle
Leena
L
Nuortio
Lauri
L
Villman
Kenneth
K
Nilsson
Greger
G
Lahtela
Sirpa-Liisa
SL
Lehtiö
Kaisa
K
Pajunen
Marjo
M
Poikonen
Paula
P
Nyandoto
Paul
P
Kataja
Vesa
V
Bono
Petri
P
Leinonen
Mika
M
Lindman
Henrik
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D043823:Taxoids / Q000008:administration & dosage
D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C508053:ERBB2 protein, human