Is epirubicin effective in first-line chemotherapy of metastatic breast cancer (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase III trial

Abstract

The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m À2 (D) with the combination of docetaxel 80 mg m À2 and epirubicin 75 mg m À2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n ¼ 26) and D arms (n ¼ 25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy. Anthracyclines are among the most active agents in the treatment of metastatic and adjuvant breast cancer (Fossati et al, 1998; EBCTCG, 2004). Docetaxel is the only agent that has demonstrated survival benefits in anthracycline-resistant patients (Nabholtz et al, 1999) and superior activity over doxorubicin as first-line chemotherapy in patients previously treated with alkylating agents (Chan et al, 1999). Owing to its activity and to the lack of crossresistance with anthracyclines, there is a strong rationale for combining docetaxel with anthracyclines. The anthracyclinetaxane regimens can now be considered the most effective regimens in metastatic breast cancer (MBC) and a first-line therapy of choice in this set of patients (Valero and Hortobagyi, 2003). In particular, many reports have described the combined use of docetaxel and epirubicin, an anthracycline less cardiotoxic than doxorubicin, with the objective to find the safest and most efficient way to integrate these classes of drugs (Mavroudis et al, 2000;Pagani et al, 2000). However, whether an anthracyclinetaxane regimen is worthy as first-line treatment for MBC patients pretreated with adjuvant or neoadjuvant anthracyclines is an open question, not definitely assessed by appropriate prospective trials. Therefore, we planned a randomised phase III trial to compare epirubicin and docetaxel vs docetaxel alone for efficacy and safety as first-line chemotherapy of MBC patients pretreated with epirubicin in adjuvant or neoadjuvant setting. MATERIALS AND METHODSEligibility criteria were: women with MBCp65 years; no previous chemotherapy for metastatic disease; measurable disease; Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2; previous adjuvant or neoadjuvant chemotherapy with anthracyclines, up to a total dose of doxorubicin p250 mg m À2 or epirubicin p500 mg m À2 , completed at least 12 months before enrollment; absence of brain metastases; adequate bone marrow, renal and liver function; left ventricular ejection fraction (LVEF) X50%. Previous adjuvant endocrine therapy as well as endocrine therapy for metastatic disease were allowed. Patients were excluded if they had received taxanes as adjuvant chemotherapy or had histo...

A phase II clinical trial of ZD1839 (Iressa™) in combination with docetaxel as first-line treatment in patients with advanced breast cancer

“…Anthracyclines and taxanes are the most active chemotherapy agents in metastatic breast cancer, with response rates in first-line combination treatment of 46-68% [3]. As anthracyclines and taxanes are increasingly used in the adjuvant setting, response rates in the metastatic setting are expected to decrease [4]. Targeting the biological properties of breast cancer has become an active focus of investigation.…”

Intra‑arterial interventional therapy for inoperable local advanced breast cancer: A retrospective study

“…However, in LABC, only a small proportion of patients may achieve PCR due to the large tumor size (14). Additionally, re-administration of anthracycline to patients with anthracycline-pretreated breast cancer may be associated with reduced efficacy and significant cardiotoxicity (15), making LABC treatment a challenge to clinical physicians and surgeons. The present study indicates that IAIT is an option for the management of older patients with LABC, particularly those with cardiac dysfunction.…”

First-Line Chemotherapy for HER-2–Negative Metastatic Breast Cancer Patients Who Received Anthracyclines as Adjuvant Treatment

“…Significant differences for the overall response rate (31% versus 11%; p ϭ .04) and median time to treatment failure (4.2 versus 2.1 months; p ϭ .001) in favor of nonpegylated liposomal doxorubicin were observed, while there was no difference in survival. Moreover, treatment with nonpegylated liposomal doxorubicin was associated with a significantly lower risk for developing cardiotoxicity as compared with con- [10]. The predictive distribution for total responses in ED is positioned on the left, in a region of substantially fewer responses than that of D; therefore, the probability of a difference in response rates favoring ED is very low.…”

“…To the best of our knowledge, only one study with a prospective design tackled the question of rechallenge with anthracycline-containing regimens [10]. It was a small randomized phase III trial comparing the efficacy of epirubicin plus docetaxel (ED) with that of docetaxel (D) alone as first-line chemotherapy of metastatic breast cancer patients pretreated with epirubicin in the adjuvant or neoadjuvant setting.…”