title: Predictive role of hand-foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer.
abstract: BACKGROUND
  Correlations between development of hand-foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial.
  
  
  METHODS
  Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV-CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV-CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed.
  
  
  RESULTS
  Among 277 patients treated with BEV-CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively.
  
  
  CONCLUSIONS
  This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV-CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.
authors.affiliation: Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, Medical University Vienna - General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria.|Central European Cooperative Oncology Group (CECOG), Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zielinski
authors.affiliation: National Institute of Oncology, Ráth György u. 7-9, H-1122 Budapest, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Lang
authors.affiliation: Institute of Oncology, Clinical Center, University of Sarajevo, Bolnicka 27, 71000 Sarajevo, Bosnia and Herzegovina.
authors.forename: Semir
authors.initials: S
authors.lastname: Beslija
authors.affiliation: Department of Oncotherapy, University of Szeged, Korányi fasor 12, H-6720 Szeged, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kahan
authors.affiliation: Oncology Division, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel.
authors.forename: Moshe J
authors.initials: MJ
authors.lastname: Inbar
authors.affiliation: Davidoff Center, Rabin Medical Center, Kaplan Street, Petah Tikva 49100, Israel.
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.affiliation: University of Medicine and Pharmacy Bucharest, Soseaua Fundeni, Nr 252, Sector 2, Bucharest 022328, Romania.
authors.forename: Rodica
authors.initials: R
authors.lastname: Anghel
authors.affiliation: Department of Medical Oncology, University Hospital Zagreb-Rebro, Medical University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.
authors.forename: Damir
authors.initials: D
authors.lastname: Vrbanec
authors.affiliation: IST GmbH, Soldnerstrasse 1, 68219 Mannheim, Germany.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.affiliation: Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, Medical University Vienna - General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria.|Central European Cooperative Oncology Group (CECOG), Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069287:Capecitabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000068258:Bevacizumab; D000069287:Capecitabine; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human