An open label RCT has examined whether integration of capecitabine into standard adjuvant chemotherapy regimens typically comprising a taxane, an anthracycline, and cyclophosphamide, for patients with moderate-to-high-risk early breast cancer, can enhance outcome.

The study involved 1500 women with axillary node-positive or high-risk node-negative breast cancer randomised to either 3 cycles of capecitabine and docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753), or to 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The primary endpoint was recurrence-free survival.

According to a planned interim analysis (modified intention to treat) carried out after 3 years' median follow-up, which excluded 2 patients in each group because of withdrawal of consent or distant metastases:

• Recurrence-free survival was better with the capecitabine regimen than with control (93% vs 89%; hazard ratio 0.66, 95% CI 0.47 to 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%]).

• The control regimen was associated 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.

The researchers conclude that capecitabine-containing chemotherapy regimen reduced breast cancer recurrence compared with a control schedule of standard agents, but capecitabine was frequently discontinued because of adverse effects.