title: Bendamustine prolongs progression-free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC.
abstract: Two i.v. regimens, bendamustine, methotrexate and 5-fluorouracil (BMF) and cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were compared as first-line therapy in a randomized, open, multicenter phase III trial including 364 patients with metastatic breast cancer (MBC). Bendamustine is an anti-neoplastic agent with alkylating, but also additional, so far unclear, mechanisms of action. We wanted to show the superiority of BMF over CMF in terms of time to progression (TTP) (primary endpoint), overall response, response duration, toxicity and quality of life (QoL). TTP was significantly longer in the BMF group (8.2 versus 6.7 months for CMF) (p=0.0071). The effect of BMF on TTP was more pronounced in the stratum 'prior adjuvant therapy, no visceral metastases' (p=0.034). Overall response rates and QoL did not significantly differ between the regimens. BMF caused more mucositis and leukopenias. Thus, bendamustine, when replacing cyclophosphamide in the CMF combination, can be expected to produce longer progression-free survival in first-line treatment of MBC.
authors.affiliation: University Women's Hospital, Frankfurt, Germany. Minckwitz@germanbreastgroup.de
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: I
authors.initials: I
authors.lastname: Chernozemsky
authors.forename: L
authors.initials: L
authors.lastname: Sirakova
authors.forename: P
authors.initials: P
authors.lastname: Chilingirov
authors.forename: R
authors.initials: R
authors.lastname: Souchon
authors.forename: N
authors.initials: N
authors.lastname: Marschner
authors.forename: U
authors.initials: U
authors.lastname: Kleeberg
authors.forename: C
authors.initials: C
authors.lastname: Tsekov
authors.forename: D
authors.initials: D
authors.lastname: Fritze
authors.forename: C
authors.initials: C
authors.lastname: Thomssen
authors.forename: N
authors.initials: N
authors.lastname: Stuart
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: S
authors.initials: S
authors.lastname: Loibl
authors.forename: Kh
authors.initials: Kh
authors.lastname: Merkle
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D011446:Prospective Studies; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009588:Nitrogen Mustard Compounds; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D005472:Fluorouracil; D008727:Methotrexate