Dr. Green said the demonstrated effectiveness of capecitabine in the metastatic setting supports its integration in the treatment of early breast cancer. This evidence is also accompanied by a favourable safety profile, with minimal myelosuppression and alopecia, she said.

Capecitabine has been shown to be highly active in combination regimens, with extended overall survival when combined with docetaxel, she said, thus defining capecitabine as a logical partner for improved outcomes in combination with taxanes in early breast cancer. This is supported by a recent Korean randomised phase 3 trial, which compared neoadjuvant capecitabine/docetaxel 1000/75 mg/m² three times weekly for four cycles (XT) versus doxorubicin/cyclophosphamide 60/600 mg/m² three times weekly for four cycles (AC), Dr. Green said.

This trial enrolled 204 patients with Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less, stage II/III breast cancer, axillary lymph node involvement and no prior treatment, who were randomised to the XT or AC regimens. Then, following surgery, patients were crossed over, from XT to AC and from AC to XT. The primary objective was a pathological complete response (pCR).

The initial treatment arms were well balanced for age, performance status, disease stage and receptor status. There were 103 subjects in the XT arm (median age, 44 years) and 101 in the AC arm (median age, 45 years).

Results showed that neoadjuvant XT was significantly more effective than AC, with clinical responses of 84% (complete, 5%; partial, 79%) and 67% (complete, 4%; partial, 63%; P = .0047), respectively. This was also seen as a breast tumour pCR of 23% versus 10%, respectively. Dr. Green also added that XT increased pCR versus AC in primary tumours and lymph nodes.

In addition, the two treatments showed comparable tolerabilities for all-grade adverse events.

Dr. Green also gave a brief summary of other trials that have demonstrated benefits of XT, with high response rates (80%-90%), and improvements as part of combination therapy in neoadjuvant breast cancer, where XT-based combinations further improved response rates (75%-100%).

Neoadjuvant capecitabine at a dose of 850 mg/m² twice daily on days 1 to 14 every 3 weeks plus radiation has shown a high level of efficacy for patients with anthracycline-resistant breast cancer, with tumour size showing a reduction from 80 cm² to 49 cm², and 82% of patients being operable after undergoing this regimen. This treatment was also well tolerated, with no grade 3/4 adverse events, Dr. Green said.

In ongoing evaluations of neoadjuvant capecitabine, Dr. Green said several randomised studies are exploring alternative doses of XT, from the previously used 1000/75 mg/m² dose, to 950/75 mg/m², 825/75 mg/m² and 900/60 mg/m². She also pointed to the German cooperative group neoadjuvant phase 3 study GEPARQUATTRO, which is evaluating sequential and combination XT 900/75 mg/m² after four cycles of epirubicin/cyclophosphamide.

Thus, Dr. Green concluded, evidence from these completed and ongoing trials indicate that the survival benefits of capecitabine should translate to the neoadjuvant setting in the treatment of early breast cancer.

This conference was sponsored by Roche.

REFERENCE:
Lee et al. Breast Cancer Res Treat, 2005, 94 (suppl. 1), S224 (Abst. 5052).


[Presentation title: What Can Xeloda Add to Neoadjuvant Chemotherapy?]

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