Sequential high-dose alkylating therapy and stem cell support for high-risk stage III breast cancer

Patients who receive neoadjuvant chemotherapy for locally advanced breast cancer and have four or more ipsilateral axillary lymph nodes involved at surgery are at high risk for recurrence, with a median time to relapse of 18 months. We offered such patients high-dose chemotherapy with stem cell rescue. Patients received cyclophosphamide or paclitaxel and granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells. Melphalan 140 mg/m2 was then given with stem cell rescue. Twenty-four to 35 days later, thiotepa 900 mg/m2 was given with stem cell rescue. Patients with hormone receptor-positive tumors received tamoxifen. We treated 14 patients in this fashion from 1995 to 1998. The mean age was 46.7 years. The majority of cancers were stage IIIB (79%). Thirteen women underwent mastectomy after anthracycline-containing chemotherapy and 50% had more than seven positive lymph nodes. Hospitalization was principally for neutropenic fever. Other morbidities were pneumonitis, cardiomyopathy, and grade 3/4 white blood cell (WBC) toxicity. No patient died of a treatment-related complication. Seven of 14 relapsed at 10, 12, <15, 15, 17, 21, and 36 months, with median follow-up of 26.5 months. Time to relapse in this small series is only modestly improved over historical experience with standard-dose adjuvant chemotherapy. Alternative strategies for treating locally advanced breast cancer should be pursued.