title: Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial.
abstract: Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(®)) and paclitaxel (Taxol(®)) alone (ET) or in combination with capecitabine (Xeloda(®), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (χ(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
authors.affiliation: Breast-Sarcoma Unit, Department of Oncology, Karolinska University Hospital, Karolinska Institutet, 17176, Stockholm, Sweden. thomas.hatschek@karolinska.se
authors.forename: T
authors.initials: T
authors.lastname: Hatschek
authors.forename: L
authors.initials: L
authors.lastname: Carlsson
authors.forename: Z
authors.initials: Z
authors.lastname: Einbeigi
authors.forename: E
authors.initials: E
authors.lastname: Lidbrink
authors.forename: B
authors.initials: B
authors.lastname: Linderholm
authors.forename: B
authors.initials: B
authors.lastname: Lindh
authors.forename: N
authors.initials: N
authors.lastname: Loman
authors.forename: M
authors.initials: M
authors.lastname: Malmberg
authors.forename: S
authors.initials: S
authors.lastname: Rotstein
authors.forename: M
authors.initials: M
authors.lastname: Söderberg
authors.forename: M
authors.initials: M
authors.lastname: Sundquist
authors.forename: T M
authors.initials: TM
authors.lastname: Walz
authors.forename: M
authors.initials: M
authors.lastname: Hellström
authors.forename: H
authors.initials: H
authors.lastname: Svensson
authors.forename: G
authors.initials: G
authors.lastname: Aström
authors.forename: Y
authors.initials: Y
authors.lastname: Brandberg
authors.forename: J
authors.initials: J
authors.lastname: Carstensen
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: J
authors.initials: J
authors.lastname: Bergh
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D017239:Paclitaxel; D005472:Fluorouracil