title: A three-arm randomized phase II study of oral vinorelbine plus capecitabine versus oral vinorelbine and capecitabine in sequence versus docetaxel plus capecitabine in patients with metastatic breast cancer previously treated with anthracyclines.
abstract: Owing to the increased number of patients treated with anthracycline-based adjuvant chemotherapy, there is a need for new effective and tolerable nonanthracycline regimens in metastatic breast cancer. Patients with HER2-negative metastatic breast cancer previously treated with anthracyclines in (neo)adjuvant setting were randomized to fully oral 3 weekly cycles of the combination of oral vinorelbine with capecitabine (V + C), to the same drugs alternating every three cycles (V↔C), or to the combination of docetaxel and capecitabine (D + C). V was given at 80 mg/m(2) (after the first cycle at 60 mg/m(2)) on days 1 and 8 in the V + C arm and weekly in the V↔C arm, C at 1,000 mg/m(2) bid from days 1 to 14, and D on day 1 at 75 mg/m(2). The primary end point was disease control rate (CR + PR + NC ≥ 3 months). A total of 139 patients were randomly assigned to V + C (44 patients), V↔C (47 patients), and D + C (48 patients). After an independent review, the disease control rate in the intent-to-treat population in the V + C, V↔C, and D + C arms [95% CI] was 70.5% [54.8-83.2], 37.0% [23.2-52.5], and 70.8% [55.9-83.1], and the median overall survival 22.2, 19.4, and 24.2 months, respectively. When taken into account the disease control rate, the alternating V↔C regimen seems to be less effective compared with V + C or D + C combinations. Combinations of V + C or D + C showed similar efficacy and a different toxicity profile; V + C induced less neutropenia, infection, hand-foot syndrome, fatigue/asthenia, and alopecia, whereas D + C - less gastrointestinal toxicity. V + C combination constitutes a valuable fully oral alternative option to D + C in patients with metastatic breast cancer previously treated with anthracyclines in (neo)adjuvant setting, while offering the advantages of an all-oral treatment.
authors.affiliation: Institut de Cancérologie de l'Ouest/René Gauducheau, Centre de Recherche en Cancérologie, UMR-INSERM 892, St Herblain, France. mario.campone@ico.unicancer.fr
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Natalya
authors.initials: N
authors.lastname: Dobrovolskaya
authors.forename: Serjei
authors.initials: S
authors.lastname: Tjulandin
authors.forename: Shin-Chen
authors.initials: SC
authors.lastname: Chen
authors.forename: Sameul
authors.initials: S
authors.lastname: Fourie
authors.forename: Fawzia
authors.initials: F
authors.lastname: Mefti
authors.forename: Maria
authors.initials: M
authors.lastname: Konstantinova
authors.forename: Florence
authors.initials: F
authors.lastname: Lefresne
authors.forename: Nadege
authors.initials: N
authors.lastname: Meheust
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D018943:Anthracyclines; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D000069287:Capecitabine; D000077235:Vinorelbine; D005472:Fluorouracil