Lancet Oncol. 2009 Nov 10;[Epub Ahead of Print], H Joensuu, P-L Kellokumpu-Lehtinen, R Huovinen, A Jukkola-Vuorinen, M Tanner, R Asola, R Kokko, J Ahlgren, P Auvinen, A Hemminki, O Paija, L Helle, L Nuortio, K Villman, G Nilsson, S-L Lahtela, K Lehtiö, M Pajunen, P Poikonen, P Nyandoto, V Kataja, P Bono, M Leinonen, H Lindman, on behalf of the FinXX Study Investigators
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.
Findings: 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.
Interpretation: 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.