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Combination Versus Sequential Doxorubicin and Docetaxel as Primary Chemotherapy for Breast Cancer: A Randomized Pilot Trial of the Hoosier Oncology Group

From the Hoosier Oncology Group and the Walther Cancer Institute, Indianapolis, IN.

Address reprint requests to Kathy D. Miller, MD, 3202 N Meridian St, Indianapolis, IN 46202-4646; email kathmill{at}iupui.edu

PURPOSE: To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhône-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/m² every 2 weeks for three cycles followed by docetaxel 100 mg/m² every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m² plus docetaxel 75 mg/m² 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 clinicallypositive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in both 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.

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