CANTON, OhioNeoadjuvant breast cancer therapy research has
revealed that epirubicin has good activity in the neoadjuvant
setting and was associated with prolonged survival in four studies,
although this remains to be confirmed, Terry Mamounas, MD,
stated. Dr. Mamounas, Medical Director at Aultman Memorial Hospital
in Canton, Ohio, spoke at the clinical investigators workshop
sponsored by the University of Texas M. D. Anderson Cancer Center and
Neoadjuvant therapy demonstrates quickly the in vivo
sensitivity of new agents and allows assessment of surrogate
biomarkers such as clinical and pathological complete response
(CR), Dr. Mamounas said. He offered several reasons why
epirubicin (Ellence) is an attractive candidate for neoadjuvant
breast cancer treatment:
the anthracyclines are very active in breast cancer;
the dose of epirubicin can be intensified; and
epirubicin is easier to combine with other agents, especially
the taxanes, than are other anthracyclines.
In a study sponsored by the European Organization for Research and
Treatment of Cancer (EORTC) and the National Cancer Institute of
Canada (NCIC), 448 patients were randomized to
epirubicin/cyclophosphamide (Cytoxan) (EC) with granulocyte colony
stimulating factor (G-CSF) or to standard CEF (cyclophosphamide,
epirubicin, 5-fluorouracil [5-FU]). The intensified EC regimen
yielded no improvement in CR rates, Dr. Mamounas reported, and no
differences in relapse-free survival or in overall survival at a
median follow-up of 30 months. Other studies, however, did show
benefits of epirubicin.
Dr. Mamounas referred to a report by Gianni Bonadonna, MD, and
colleagues from Italy at the American Society of Clinical Oncology
(ASCO) annual meeting that neoadjuvant treatment with single-agent
epirubicin permitted effective down-staging of many tumors and
permitted more women to undergo breast-conserving surgery. The 4-year
results from that trial showed a 68% overall response rate with
single-agent epirubicin. According to Dr. Mamounas, this is
comparable to results with the standard doxorubicin
(Adriamycin)/cyclophosphamide (AC) regimen. Sixty-seven percent of
patients were able to undergo breast-conserving surgery.
This trial shows that we have to make very sure our margins are
negative in surgery after neoadjuvant therapy, Dr. Mamounas
said. The risk of ipsilateral relapse was 13.9% in patients with
positive margins and 2.9% in those with negative margins (P =
A French phase II trial compared FEC-100 (5-FU 50 mg/m²,
cyclophosphamide 500 mg/m², plus epirubicin 100 mg/m²) with
epirubicin/docetaxel (Taxotere) (ED) as neoadjuvant regimens.
Forty-eight patients in each group were evaluable for toxicity. Grade
3-4 neutropenia was more common in the ED group, Dr. Mamounas
reported, but was generally brief and manageable with growth factors.
There were no instances of congestive heart failure (CHF) in the ED
group and 3 in the FEC group.
Overall response rates and pathological response in the lymph nodes
were similar. The objective response rate was 81% with ED vs 55% with
FEC-100, but Dr. Mamounas warned that this was a small phase II trial
and needs to be confirmed in larger randomized studies.
Weekly neoadjuvant ED has also been studied in a phase I trial in 23
patients. Patients were treated with 30 mg/m² of epirubicin and
35 mg/m² of docetaxel once weekly. The overall response rate was
88%, Dr. Mamounas said, and 56% of patients had sufficient tumor
shrinkage to permit breast-conserving surgery.
Infusional epirubicin/cisplatin/5-FU (ECisF) has been compared to AC
in a phase III trial in 426 patients. Dr. Mamounas reported that the
clinical response rate was very encouraging at a median follow-up of
30 months, but whether this means anything needs to be seen.
Patients on the infusional therapy experienced greater toxocity and
required more treatment delays and dosage reductions.
Clearly, this is a tough regimen to use in the
neoadjuvant setting, Dr. Mamounas said.
The influence of cancer susceptibility genes is increasingly coming
into play in designing breast cancer therapy, and Dr. Mamounas
discussed a trial of the response to neoadjuvant FEC-50 (with
epirubicin 50 mg/m²) vs FEC-100 in women with HER2/neu-positive
breast cancer. The conclusion was that if you are HER2/neu
positive, you should get the higher dose regimen, he stated.