title: Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design.
abstract: OBJECTIVE
  To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer.
  
  
  METHODS
  Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study.
  
  
  RESULTS
  The groups were well balanced with respect to prognostic factors. Time to progression did not differ in the comparison between CDDP arms and non-CDDP arms (median, 10.9 months v 9.4 months, respectively; P =.10) or between that of LND arms and non-LND arms (median, 10.8 months v 9.9 months, respectively; P =.47), nor did overall survival. The response rate did not significantly differ in the comparison between LND arms and non-LND arms (62.9% v 54.0%, P =.08). No difference in treatment activity was observed between CDDP arms and non-CDDP arms. Toxicity was significantly higher in the CDDP arms, leading to CDDP dose adjustment in 40% of cases. The most frequent side effects were of a hematologic and gastrointestinal nature. The addition of LND produced more myalgias and fatigue.
  
  
  CONCLUSIONS
  Neither CDDP nor LND was able to significantly improve the time to progression obtained by EPI. CDDP, however, significantly worsened the drug's tolerability.
authors.affiliation: Oncologia Medica, Azienda Ospedaliera San Luigi, Orbassano, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bitossi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gorzegno
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.forename: Palmiro
authors.initials: P
authors.lastname: Alquati
authors.forename: Andrea
authors.initials: A
authors.lastname: De Matteis
authors.forename: Francesco
authors.initials: F
authors.lastname: Nuzzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giardina
authors.forename: Saverio
authors.initials: S
authors.lastname: Danese
authors.forename: Mario
authors.initials: M
authors.lastname: De Lena
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Antonio
authors.initials: A
authors.lastname: Farris
authors.forename: Maria Giuseppa
authors.initials: MG
authors.lastname: Sarobba
authors.forename: Enza
authors.initials: E
authors.lastname: DeFabiani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bonazzi
authors.forename: Federico
authors.initials: F
authors.lastname: Castiglione
authors.forename: Cesare
authors.initials: C
authors.lastname: Bumma
authors.forename: Gregorio
authors.initials: G
authors.lastname: Moro
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Luigi
authors.initials: L
authors.lastname: Dogliotti
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage; D016015:Logistic Models; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D007191:Indazoles; D015251:Epirubicin; D002945:Cisplatin; C016371:lonidamine