Clinical and pharmacokinetic data of a docetaxel-epirubicin combination in metastatic breast cancer

Abstract

In order to explore activity and pharmacokinetic data of a docetaxel-epirubicin combination we analyzed a population of 60 metastatic breast cancer patients. All the patients had an ECOG performance status < 3; 41 patients (68%) had visceral metastases as dominant site of disease, including 33% with liver metastases. Three or more involved organs were present in 43% of patients; 35% had received prior hormonotherapy; 10% for metastatic disease. Twenty-five patients (42%) had received prior adjuvant chemotherapy; 15% a CAF regimen. Twenty per cent of patients had less than 12 months disease-free interval. Docetaxel and epirubicin were both given at a dose of 75 mg/m2 i.v. d. 1 every 3 weeks. After a median of six cycles we had 5 CR (8.3%), 40 PR (66.6%), 7 NC (11.6%), and 8 PD (13.3%). Response rates in patients with visceral and liver metastases were 78% and 55% respectively. Premenopausal status, < 1 year disease free survival and > 3 metastatic sites were associated with a lower response rate. After a median follow-up of 19 months (12-36), median disease-free survival is 11 months and median overall survival has not been reached. Grade 4 neutropenia was observed in 75% of courses but with febrile neutropenia in 6.2% of courses only. Non-hematologic toxicity wasn't clinically important. A NYHA class III reversible cardiac failure was observed in one patient (1.6%). The pharmacokinetic evaluation in 16 patients has shown that docetaxel transiently interfered with epirubicin plasma level when docetaxel was administered 1 h after epirubicin.

First Efficacy Results of Capecitabine with Anthracycline- and Taxane-Based Adjuvant Therapy in High-Risk Early Breast Cancer: A Meta-Analysis

“…From previous trials, we have found fewer adverse reactions with docetaxel and capecitabine compared with anthracycline or paclitaxel [7], [24], [25]. To some extent, addition of capecitabine did not significantly increase the toxicity, except for diarrhea and hand–foot syndrome related to capecitabine, but it might have reduced neutropenia and febrile neutropenia, which could have been due to reduced dose of docetaxel [3].…”

A Phase II Study of Docetaxel and Epirubicin in Advanced Adult Soft Tissue Sarcomas (STS)

“…Docetaxel was administered at the maximum accepted dose according to pharmacokinetic studies. 21,22 Therefore, this study seems to provide the best results that can be obtained in terms of dose-response effect. In addition, dose escalation of epirubicin could possibly increase the risk of cardiotoxicity.…”

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer

“…Overall response rates of 57 -79% were reported with 3-weekly combinations of docetaxel 60 -80 mg m À2 in five first-line noncomparative studies in a total of 170 patients with metastatic breast cancer (Sparano et al, 2000;Baltali et al, 2001;Lippe et al, 2002;Aihara et al, 2003;Morales et al, 2004). Previous noncomparative studies of 3-weekly epirubicin 75 mg m À2 plus docetaxel 75 mg m À2 have yielded overall tumour response rates of 67 -84%, with overall survival of up to approximately 2 years (Airoldi et al, 2001;Yeo et al, 2002;Morales et al, 2004).…”

“…Haematologic adverse events (most notably neutropenia) were most common, with no excessive cardiac toxicity or any indication that the addition of docetaxel to doxorubicin increases the cardiotoxicity of the latter (Sparano et al, 2000;Baltali et al, 2001;Lippe et al, 2002;Aihara et al, 2003;Morales et al, 2004). In one phase II noncomparative trial of epirubicin and docetaxel, no grade 4 nonhaematologic adverse events and very low levels of cardiotoxicity (reversible congestive heart failure in one of 60 patients only) were observed (Yeo et al, 2002), whereas in another study there was no grade 3 -4 cardiac toxicity and no treatment-related mortality among 46 patients (Airoldi et al, 2001). A further recent trial of 133 patients reported that two withdrew treatment due to cardiotoxicity, although none developed congestive heart failure (Morales et al, 2002).…”

“…Epirubicin is an anthracycline that may be less cardiotoxic than doxorubicin, and noncomparative phase II studies have shown very encouraging responses to treatment when this drug is combined with docetaxel as first-line therapy in metastatic breast cancer (French Epirubicin Study Group, 1998;Airoldi et al, 2001;Morales et al, 2002;Pharmacia Corporation, 2002;Yeo et al, 2002). The present randomised phase II study evaluated epirubicin 75 mg m À2 plus docetaxel 75 mg m À2 (ET) and the standard FEC triple combination, using the same dose of epirubicin (75 mg m À2 ).…”