MUNICH—Preoperative treatment of primary breast cancer with dose-dense sequential epirubicin(Drug information on epirubicin) (Ellence) and paclitaxel(Drug information on paclitaxel) (Taxol) led to significant increases in breast-conserving therapy and in response rates compared to epirubicin and paclitaxel at standard doses. A prospective randomized, controlled clinical trial conducted at multiple centers in Germany also found comparable toxicity between the two regimens (ASCO abstract 133).
After successful prior studies in the adjuvant setting, the trial was conducted in the neoadjuvant setting for four main reasons, stated the study’s lead investigator Michael Untch, MD, of Klinikum Grosshadern in Munich.
- Survival equivalence was demonstrated between preoperative and postoperative treatment.
- Retrospective and prospective evidence show increased rates of breast conserving surgery with neoadjuvant treatment.
- The pathologic complete response rate, defined by Dr. Untch as "no evidence of invasive cancer at primary tumor site," is a very good surrogate predictor of improved outcome.
- The preoperative setting provides a good model for investigating dose-dense chemotherapy.
Surgery After Chemotherapy
Speaking on behalf of the AGO Study Group (Arbeitsgemeinschaft Gynaekologische Onkologie), Dr. Untch said that patients received treatment with anthracyclines and taxanes, the two most potent classes of chemotherapeutic agents. They were randomly assigned to receive either: epirubicin at 150 mg/m², followed by paclitaxel at 250 mg/m², both 3 times every 2 weeks, with G-CSF (filgrastim) support (5 µg/kg/d) on days 3 to 10; or to receive epirubicin at 90 mg/m² and paclitaxel at 175 mg/m², 4 times every 3 weeks, as preoperative therapy.
For both groups, surgery was performed after completion of chemotherapy. All patients received CMF (cyclophosphamide, methotrexate(Drug information on methotrexate), fluorouracil(Drug information on fluorouracil)) 3 times every 4 weeks after surgery. Locoregional radiotherapy was also mandatory. Also, hormone receptor positive (HR+) patients received tamoxifen(Drug information on tamoxifen).
Included patients (n = 549, median age 50 years) had primary breast cancer (T > 3 cm or inflammatory disease) diagnosed by core biopsy and adequate clinical performance status (96.5% with Eastern Cooperative Oncology Group [ECOG] status 0). About 53% were premenopausal. The median tumor diameter was 4.2 cm (range 3.0-8.5 cm), and 16% of all patients had inflammatory disease. "We are dealing with large tumors, here," Dr. Untch commented. Fourteen and one-half percent had inflammatory disease.
Mastectomy was proposed in 74.5% of cases, and 64.5% were clinical node positive. Dr. Untch underscored that assessment was conducted not just by clinical palpation, but by mammography, MRI, and ultrasound before neoadjuvant therapy and before surgery.
