A phase II study of second-line neoadjuvant chemotherapy with capecitabine and radiation therapy for anthracycline-resistant locally advanced breast cancer

Objective: According to data from Brazil's National Cancer Institute nearly 30% of the new patients who present with breast cancer have locally advanced disease. These patients are inoperable and tumor reduction is usually attempted with chemotherapy. First-line anthracyclin-based neoadjuvant chemotherapy is often effective; however, about 30% of the patients fail and to date there is no established second-line treatment. We have studied the concomitant use of radiation therapy and capecitabine in this setting, to determine the toxicity and efficacy of this regimen as a second-line neoadjuvant treatment. Patients and Methods: Twenty-eight patients with inoperable locally advanced breast cancer refractory to first-line anthracycline based treatment were enrolled between January 2003 and May 2004. Patients received radiation therapy (50 cGy) and concomitant capecitabine (850 mg/m(2)) twice daily for 14 days every 3 weeks. Results: This treatment rendered 23 of the 28 patients (82%) operable. The 5 remaining patients did not undergo surgery because of disease progression. The median clinical tumor size decreased from 80 cm(2) to 49 cm(2). Microscopic residual disease was observed in 3 patients (13%) and another patient achieved a complete pathologic response. The median number of involved lymph nodes was 2 and treatment was well tolerated with no grade 3 or 4 events. Conclusion: Our data indicate that second-line neoadjuvant treatment with radiation therapy and capecitabine is feasible, well tolerated, and effective in patients with locally advanced breast cancer refractory to primary anthracycline-based treatment. These results suggest that a randomized study should be done to compare radiotherapy alone to capecitabine combined with radiotherapy.