Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: A randomized pilot trial of the Hoosier Oncology Group

Purpose: To evaluate the efficacy and toxicity of combination and sequential dose dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhone-Poulenc Rorer Collegeville, PA) as primary chemotherapy of breast cancer. Patients and Methods: patients with newly diagnosed stage II or noninflammatory stage III breast cancer were randomly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery. Patients in arm A received sequential therapy with doxorubicin 75 mg/m(2) every 2 weeks for three cycles followed by docetaxel 100 mg/m(2) every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks for four cycles. Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups. Results: Forty patients were entered onto the trial. Pretreatment tumor size averaged 5.7 cm with clinically positive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, greater than or equal to 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in bath groups, with an overall response rate of 87%, including 20% clinical complete remissions. Pathologic complete remission or residual in situ disease only was confirmed in five patients (12.8%). patients who received sequential therapy had fewer positive lymph nodes (mean, 2.17 v 4.81: P < .037) at definitive surgery. Conclusion: Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active. A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy. (C) 1999 by American Society of Clinical Oncology.