A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel and sorafenib in women with node-positive or high-risk early-stage breast cancer.

Purpose: To examine the safety of sorafenib combined with standard adjuvant treatment in patients with node-positive or otherwise high-risk breast cancer. Patients and Methods: Eligibil- ity: mastectomy/breast-conserving surgery; axillary node assessment for stage I/II/IIIA/IIIC (T1-3, N3a only) breast cancer; node-positive/ high-risk node-negative (tumor size >2 cm; hormone-receptor negative; grade 2/3; or age <35 years); Eastern Cooperative Oncol- ogy Group performance status (ECOG-PS) 0-1; and adequate organ function. Treatment: doxorubicin (60 mg/m2 intravenous) and cyclophosphamide (600 mg/m2 intravenous; AC) on day 1, every 3 weeks (x 4 cycles), followed by paclitaxel 175 mg/m 2 intravenous on day 1, (every 3 weeks x 4 cycles) or 80 mg/m2 intravenous (every week/x 12 cycles), combined with sorafenib (400 mg oral twice a week; TS) for 12 months or less. Results: Forty-five patients were enrolled from 5/07-1/08. Baseline characteristics included: median age of 54 years (range, 35-74 years); 93% of patients with ECOG-PS 0; 84% node-positive; 33% hormone-receptor negative. All patients completed AC treatment and were eligible to receive TS; of these, 8 (13%) patients came off study due to physician/patient decision; 21 (47%) patients came off study due to toxicity; 2 (4%) patients completed TS but did not proceed with maintenance sorafenib; and 14 (31%) patients completed TS and entered the maintenance phase of sorafenib treatment. Sorafenib was taken for 6.1 weeks during the paclitaxel phase and 15 weeks during maintenance. Severe toxici - ties during sorafenib therapy were limited, including neutropenia, anorexia, arthralgia, diarrhea, and dyspnea. After a median follow-up of 21.0 months (range, 18.9-25.9), all patients were alive and with- out recurrence. Conclusion: Sorafenib was generally associated with limited severe toxicity when combined with paclitaxel following AC. However, many patients discontinued sorafenib early due to grade 1/2 toxicity, physician/patient decision, and treatment compliance. Additional studies of sorafenib in breast cancer in the neoadjuvant and triple-negative settings are warranted.