title: Randomised phase 3 open-label trial of first-line treatment with gemcitabine in association with docetaxel or paclitaxel in women with metastatic breast cancer: a comparison of different schedules and treatments.
abstract: BACKGROUND
  This open-label study compared docetaxel/gemcitabine vs. paclitaxel/gemcitabine and a weekly (W) vs. 3-weekly (3 W) schedule in metastatic breast cancer (MBC).
  
  
  METHODS
  Patients relapsed after adjuvant/neoadjuvant anthracycline-containing chemotherapy were randomized to: A) gemcitabine 1000 mg/m2 Day 1,8 + docetaxel 75 mg/m2 Day 1 q3W; B) gemcitabine 1250 mg/m2 Day 1,8 + paclitaxel 175 mg/m2 Day 1 q3W; C) gemcitabine 800 mg/m2 Day 1,8,15 + docetaxel 30 mg/m2 Day 1,8,15 q4W; D) gemcitabine 800 mg/m2 Day 1,15 + paclitaxel 80 mg/m2 Day 1,8,15 q4W. Primary endpoint was time-to-progression (TTP). Secondary endpoints were overall survival (OS) and overall response rate (ORR).
  
  
  RESULTS
  Interim analysis led to accrual interruption (241 patients enrolled of 360 planned). Median TTP (months) was 8.33 (95% CI: 6.19-10.16) with W and 7.51 (95% CI: 5.93-8.33) with 3 W (p=0.319). No differences were observed in median TTP between docetaxel and paclitaxel, with 85.6% and 87.0% of patients progressing, respectively. OS did not differ between regimens/schedules. ORR was comparable between regimens (HR: 0.882; 95% CI: 0.523-1.488; p=0.639), while it was significantly higher in W than in the 3 W (HR: 0.504; 95% CI: 0.299-0.850; p=0.010) schedule. Grade 3/4 toxicities occurred in 69.2% and 71.9% of patients on docetaxel and paclitaxel, and in 65.8% and 75.2% in W and 3 W.
  
  
  CONCLUSIONS
  Both treatment regimens showed similar TTP. W might be associated with a better tumour response compared with 3 W.
  
  
  BACKGROUND
  Clinicaltrial.gov ID NCT00236899.
authors.affiliation: IRCCS AOU San Martino - IST - National Institute for Cancer Research, UO Sviluppo Terapie Innovative, Genoa, Italy. lucia.delmastro@istge.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.forename: Mauro
authors.initials: M
authors.lastname: Mansutti
authors.forename: Michele
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: Antonio
authors.initials: A
authors.lastname: Durando
authors.forename: Domenico Franco
authors.initials: DF
authors.lastname: Merlo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Ignazia
authors.initials: I
authors.lastname: La Torre
authors.forename: Matteo
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Gbenga
authors.initials: G
authors.lastname: Kazeem
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchi
authors.forename: Davide
authors.initials: D
authors.lastname: Boy
authors.forename: Marco
authors.initials: M
authors.lastname: Venturini
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
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*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D018447:Medical Futility; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D010349:Patient Compliance; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D017239:Paclitaxel; D000093542:Gemcitabine
references.citation: Oncologist. 2005 Oct;10(9):665-85
references.pmid: 16249346
references.citation: J Clin Oncol. 2009 Apr 10;27(11):1753-60
references.pmid: 19273714
references.citation: Ann Oncol. 2004 Sep;15(9):1358-65
references.pmid: 15319242
references.citation: J Clin Oncol. 2011 Dec 20;29(36):4748-54
references.pmid: 22084374
references.citation: Ann Oncol. 2011 Sep;22 Suppl 6:vi25-30
references.pmid: 21908499
references.citation: Br J Cancer. 1990 Dec;62(6):1034-8
references.pmid: 2257209
references.citation: Cancer Treat Rev. 2010 Feb;36(1):69-74
references.pmid: 19945225
references.citation: J Clin Oncol. 2002 Jun 15;20(12):2812-23
references.pmid: 12065558
references.citation: Anticancer Res. 2008 Mar-Apr;28(2B):1245-58
references.pmid: 18505062
references.citation: Breast. 2013 Jun;22(3):314-9
references.pmid: 22901442
references.citation: J Clin Oncol. 2008 Apr 1;26(10):1642-9
references.pmid: 18375893
references.citation: J Clin Oncol. 2008 Aug 20;26(24):3950-7
references.pmid: 18711184