title: Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis.
abstract: BACKGROUND
  Chemotherapy dose delay and/or reduction lower relative total dose intensity (RTDI) and may affect short- and long-term outcome of metastatic breast cancer (MBC) patients.
  
  
  METHODS
  Based on 933 individual patients' data of from 3 randomized MBC trials using an anthracycline and taxane we examined the impact of RTDI on efficacy and determined the lowest optimal RTDI for MBC patients.
  
  
  RESULTS
  Median time to disease progression (TTDP) and overall survival (OS) of all patients were 39 and 98 weeks. Overall higher RTDI was correlated with a shorter TTDP (log-rank p = 0.0525 for 85% RTDI cut-off). Proportional hazards assumption was violated, there was an early drop in the TTDP-curve for the high RTDI group. It was explained by the fact that patients with primary disease progression (PDP) do have a high RTDI per definition. Excluding those 114 patients with PDP the negative correlation between RTDI and TTDP vanished. However, non-PDP patients with RTDI-cut-off levels <85% showed a shorter OS than patients with higher RTDI levels (p = 0.0086).
  
  
  CONCLUSIONS
  Optimizing RTDI above 85% appears to improve long-term outcome of MBC patients receiving first-line chemotherapy. Lowering RTDI had no negative influence on short term outcome like OR and TTDP.
authors.affiliation: German Breast Group, Neu-Isenburg, Germany. sibylle.loibl@germanbreastgroup.de
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Tomas
authors.initials: T
authors.lastname: Skacel
authors.forename: Valentina
authors.initials: V
authors.lastname: Nekljudova
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Lück
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwenkglenks
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.forename: Christoph
authors.initials: C
authors.lastname: Zielinski
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D000093542:Gemcitabine