title: Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALT trial (phase I-II).
abstract: BACKGROUND
  Through different pharmacodynamic-kinetic interactions, weekly administration of proved efficacy agents can overcome resistance with lower toxicity and greater benefit. Based on this assumption, we designed a phase I-II trial with weekly non-pegylated liposomal anthracycline and taxane in first-line breast cancer patients.
  
  
  METHODS
  We enrolled 56 previously untreated metastatic breast cancer patients; they were randomly assigned to receive paclitaxel (Taxol) (50 mg/mq) or docetaxel (Taxotere) (30 mg/mq) combined with non-pegylated liposomal anthracycline (25 mg/mq) on days 1, 8 and 15 every 4 weeks. The primary end points were the clinical benefit and treatment-related toxic effects assessment. Secondary end points were time-to-disease progression (TTP) and overall survival (OS).
  
  
  RESULTS
  The overall clinical benefit was 87.04%. World Health Organization G3-4 toxic effects included neutropenia (45%), anemia (44%), complete alopecia (83%), severe onycholysis and neuropathy. The 24% of patients developed left ventricular ejection fraction reduction but none >10% with recover after treatment completion. The median absolute decrease from baseline was 1%. Median TTP was 11 months and median OS was 23 months.
  
  
  CONCLUSIONS
  Combined weekly administration of taxane and non-pegylated liposomal anthracycline is well tolerated and clinical benefit data encourage phase III study design.
authors.affiliation: Department of Oncology A, Policlinico Umberto, Sapienza University of Rome, 155 V.le del Policlinico, 00161 Rome, Italy. sofiarosati@tiscali.it
authors.forename: M S
authors.initials: MS
authors.lastname: Rosati
authors.forename: C
authors.initials: C
authors.lastname: Raimondi
authors.forename: G
authors.initials: G
authors.lastname: Baciarello
authors.forename: P
authors.initials: P
authors.lastname: Grassi
authors.forename: S
authors.initials: S
authors.lastname: Giovannoni
authors.forename: E
authors.initials: E
authors.lastname: Petrelli
authors.forename: M L
authors.initials: ML
authors.lastname: Basile
authors.forename: M
authors.initials: M
authors.lastname: Girolami
authors.forename: M
authors.initials: M
authors.lastname: Di Seri
authors.forename: L
authors.initials: L
authors.lastname: Frati
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D004317:Doxorubicin