GYEONGGI, KOREA-In stage II/III breast cancer, neoadjuvant docetaxel(Drug information on docetaxel) (Taxotere)/capecitabine (Xeloda) (TX) appears to offer improved clinical and pathologic complete response rates vs doxorubicin(Drug information on doxorubicin) (Adriamycin)/cyclophosphamide (Cytoxan/Neosar) (AC), preliminary phase III trial data suggest (abstract 607). Tumor response was seen in 91% of evaluable patients on TX vs 74% of patients on AC, reported investigator Hong Gi Lee, MD, of the Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea. In addition, pathologic complete response (pCR) in primary tumors was 23% for TX vs 6% for AC. A pCR of 23% is "consistent with best rates reported from other neoadjuvant trials of double combinations," Dr. Lee said. "Lack of pathologic complete response is a surrogate marker of poor survival benefit, and our results show that the docetaxel and capecitabine(Drug information on capecitabine) combination achieved a pCR higher than with an anthracycline regimen." The preliminary results come from a trial in which patients with treatment- naive stage II/III breast cancer are randomized to either TX or AC, followed by surgery, then a crossover to the opposite treatment arm: patients randomized to TX preoperatively go on to receive AC after surgery, whereas patients randomized to AC then receive TX. The rationale for using docetaxel/ capecitabine as primary chemothera- py for breast cancer comes from several lines of evidence suggesting benefit. Dr. Lee noted that docetaxel use is increasing in the primary setting, based on studies such as the NSABP (National Surgical Adjuvant Bowel Project) Protocol B-27, which suggested that adding docetaxel to AC preoperatively significantly increased clinical and pathologic response rates (J Clin Oncol 21:4165-4174, 2003). Capecitabine has been shown to be effective and well tolerated as a single agent in metastatic breast cancer, while the docetaxel/capecitabine combination extended survival, response rate, and time to progression in a phase III trial by O'Shaughnessy et al. (J Clin Oncol 20:2812-2823, 2002). To compare the efficacy and toxicity of AC and TX as primary chemotherapy for stage II/III breast cancer, Dr. Lee and colleagues enrolled 121 patients (mean age 44 years, approximately 60% stage II) who had received no prior chemotherapy, hormonal therapy, radiation, or surgery. All patients had positive axillary lymph nodes and good performance status (ECOG [Eastern Cooperative Oncology Group] 0 or 1). The preoperative treatment regimens were given every 3 weeks for four cycles. The TX arm consisted of docetaxel (75 mg/m2 in a 1-hour infusion on day 1) and capecitabine (1,000 mg/m2 PO twice daily on days 1-14). The AC arm consisted of doxorubicin (60 mg/m2 IV on day 1) plus cyclophosphamide(Drug information on cyclophosphamide) (600 mg/m2 IV on day 1). After surgery, patients crossed over to the opposite arm and received further radiation with or without tamoxifen(Drug information on tamoxifen). Interim Analysis At ASCO, Dr. Lee presented an interim analysis on 100 patients who have completed surgery. Complete or partial response was higher in TXtreated vs AC-treated patients (see Table 1). In the TX arm, 9% had stable disease vs 17% in the AC arm, in which 9% of patients had progressive disease. The TX arm also had increased pCR vs AC, both in primary tumors (23% vs 6%) and in lymph nodes (34% vs 28%). According to Dr. Lee, TX appeared to be as effective in HER2+ tumors as in HER2- tumors. Tumor and lymph node downstaging was also reported. Patients on TX had a 69% reduction in median tumor length, compared with 45% for AC-treated patients; likewise, there was an 82% reduction in lymph node size for TX, and a 62% reduction for AC. Also, the TX regimen caused less nausea and vomiting vs AC, but it led to more myalgia, skin toxicities, and nail changes. Recruitment in this trial is ongoing; according to investigators, final data should be available in about 1 year. "The final results are awaited with interest to determine whether or not nonanthracycline-based primary therapy is effective and well-tolerated in stage II/III breast cancer," Dr. Lee said. This study was supported by Aventis Pharma, Roche Korea, and a grant from the National Cancer Center, Korea.