Second-line neoadjuvant vinorelbine and gemcitabine combination in locally advanced breast cancer showing no early response to TAC.

Due to socioeconomic issues, locally advanced breast cancer (LABC) is still a common presentation of breast cancer in the third world. It was found that LABC patients showing a clinical response after two to four cycles of neoadjuvant chemotherapy have a higher probability of obtaining a pathological complete response at surgery than patients without an early response. In the present work, the short-term effects and toxicity of the neoadjuvant second-line vinorelbine and gemcitabine combination were evaluated in the treatment of LABC who did not show early response to anthracyclines and taxanes-containing regimen. The use of vinorelbine and gemcitabine was based on their use in metastatic breast cancer cases who had been treated before with anthracyclines and taxanes. This was a prospective phase II study accomplished at the Clinical Oncology and Nuclear Medicine Department of Mansoura University, Egypt. Seventy LABC patients not suitable for breast conservative surgery who failed to achieve early response to two cycles of a combination of docetaxel, doxorubicin, and cyclophosphamide (TAC) were treated with a 3-weekly regimen of vinorelbine 30 mg/m(2) plus gemcitabine 1,200 mg/m(2) given on days 1 and 8 by intravenous infusion as a second-line neoadjuvant chemotherapy. Response was assessed after the second cycle. Stable and progressed patients were operated upon while responding cases received up to four cycles before the operation. Patient accrual was from June 20, 2007, to October 20, 2009. The objective response was evaluated clinically with breast sonography before every new cycle and before operation while the pathological response was determined postoperatively. The toxicity was evaluated according to the National Cancer Institute--Common Toxicity criteria version 3. The end points of this study were clinical response rate, pathological response rate, and treatment toxicity. Clinical response rate was achieved in 35 cases (50%) while pathological response rate was reported in 4 cases (5.7%). Breast conservative surgery (BCS) became possible in 31 cases (44%). The most common severe toxicities (grades 3 and 4) were neutropenia and thrombocytopenia in 25.7 and 22.8% of cases, respectively. Toxicities were reversible and did not cause death. It is possible to achieve objective clinical and pathological responses of LABC with potentially non-cross-resistant neoadjuvant second-line therapy, leading to BCS in a high proportion of patients. Thus, preoperative second-line chemotherapy appears to be justified when breast conservation is an important treatment goal.