Welcome to PeerView

SECTION II: Neoadjuvant Therapy

Abstract 196
Neoadjuvant Herceptin/Taxotere/Cisplatin in the Treatment of Locally Advanced and Inflammatory Breast Cancer
Judith Hurley, MD, University of Miami; Taylor Breast Health Center, Jackson Memorial Hospital, Miami, Florida

The combination of trastuzumab (Herceptin) plus Taxotere (docetaxel) and cisplatin (Platinol, Asiplatin) proved to be a highly active neoadjuvant regimen in locally advanced breast cancer (stage IIB, IIIA, and IIIB) in this phase II study. Approximately 26% of patients achieved a pathologic complete response (pCR) and 50% were rendered node negative at surgery.

"Nodal status is the most important prognostic indicator, and 50% of patients in this study were rendered node negative. The high rate of negative nodes may point to a different mode of action when trastuzumab (Herceptin) is added to chemotherapy. Hopefully, these results will translate to improved survival," said Dr. Judith Hurley during a presentation at the 38^th annual ASCO meeting.

Approximately 20% to 30% of women with breast cancer have tumors that overexpress the human epidermal growth factor 2 (HER-2)/neu protein, which is associated with a poor prognosis. Trastuzumab blocks HER-2/neu receptors on the cell surface, and previous studies have shown that Taxotere and cisplatin are both synergistic with trastuzumab in vitro.

"This novel combination in the neoadjuvant setting was designed to take advantage of this synergy in hopes of improving response rates, and ultimately survival, in women with early-stage breast cancer," Dr. Hurley explained.

Trial Design
The study included 36 patients with locally advanced breast cancer that overexpressed HER-2. The median age was 52 years (range, 29-66), and 17 patients were premenopausal. At baseline, the median tumor diameter was 8 cm (range, 4-37 cm). Ten patients (28%) had no involved lymph nodes, 15 (42%) were N1, and 11 (30%) were N2. Seven (19%) were clinical stage IIB, 20 (56%) were stage IIIA, eight (22%) were stage IIIB, and one (3%) was stage IV.

The neoadjuvant regimen included trastuzumab 4 mg/kg on day 1, followed by 2 mg/kg every week for 11 weeks, plus Taxotere and cisplatin, both at a dose of 70 mg/m² on days 1, 22, 43, and 64. Patients also received growth factor support with granulocyte-colony stimulating factor (G-CSF; Neupogen) 5 痢/kg on days 2, 23, 44, 65, until the white blood cell count was greater than 10,000 cells/mm³, and epoetin alfa (Epogen, E.P.O., Eprex, Erythropoietin, Procrit) 40,000 units/mL every week for 12 weeks. Following surgery, patients received doxorubicin (Adriamycin, Adiblastine, Adriablatina, Doxil, and others) and cyclophosphamide (Cytoxan, Cytokan, Endoxon, Neosar, Neosar For Injection) plus G-CSF support. Patients with estrogen receptor-positive (ER+) tumors received tamoxifen 20 mg daily for five years.

Results
Following neoadjuvant therapy, nine women (26%) achieved a pCR with no evidence of invasive tumor (Table 2). Fifty percent of patients were rendered node negative.

Table 2. Pathologic Complete Response to Neoadjuvant Therapy in Locally Advanced Breast Cancer

Table 2. Pathologic Complete Response to Neoadjuvant Therapy in Locally Advanced Breast Cancer

Source: Adapted from Judith Hurley, MD, as presented at the 38^th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 18-21, 2002, Orlando, Florida. Abstract 196.

Toxicity
Thirty-three patients were evaluable for toxicity. Grade 3 and 4 hematologic toxicity was acceptable, with only two patients (6%) experiencing grade 3 or 4 leukopenia and no patients experiencing grade 3 or 4 anemia, Dr. Hurley said. The most common non-hematologic grade-3/4 toxicity was hyperglycemia, experienced by 11 (33%) patients. Other grade 3 toxicities were nausea/vomiting in two (6%), anxiety/depression in one (3%), and catheter infection in two (6%). No grade 3 or 4 alopecia, anemia, asthenia, diarrhea, renal insufficiency, rash, bone pain, or edema was observed.

Two of 34 (6%) patients evaluated for cardiotoxicity experienced a decrease in left ventricular ejection fraction.

Key Points In Focus:

The combination of trastuzumab, Taxotere and cisplatin as neoadjuvant therapy was highly active in locally advanced breast cancer (stage IIB, IIIA, and IIIB) in this phase II study.
A pCR was obtained in 26% of patients following neoadjuvant therapy, and 50% of patients were rendered node negative at the time of surgery.

--[ TOP ]--