title: The combination of a chemotherapy doublet (gemcitabine and capecitabine) with a biological doublet (bevacizumab and erlotinib) in patients with advanced pancreatic adenocarcinoma. The results of a phase I/II study.
abstract: BACKGROUND
  Preclinical data support the combined inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways in the treatment of pancreatic cancer. Following a dose finding phase I study the efficacy and toxicity of a four-drug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine (GemCap), with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer.
  
  
  METHODS
  In a phase II expansion cohort, patients with chemonaive locally advanced or metastatic pancreatic cancer received gemcitabine (1000mg/m(2) D1, 8, 15), capecitabine (1400mg/m(2) D1-21), erlotinib (100mg daily) and bevacizumab (5mg/kg D1, 15) every 28days. The primary endpoint was radiological response rate by response evaluation criteria in solid tumours (RECIST). Computed tomography (CT) assessment was performed every 8weeks. Consolidation radiotherapy was considered in locally advanced patients following six cycles of treatment.
  
  
  RESULTS
  In total 44 patients (phases I & II) were recruited. The median cycles delivered were 6 (range 1-16). Confirmed radiological responses were seen in 23% (95% confidence interval (CI): 11-38%) of patients. The median progression-free and overall survival for the entire cohort was 8.4 and 12.6months, respectively. In patients with metastatic disease the median overall survival was 10.1months. Common grade 3/4 toxicities were; neutropenia 52%, lethargy 32%, diarrhoea 18% and hand-foot syndrome 18%.
  
  
  CONCLUSIONS
  The combination of gemcitabine, capecitabine, erlotinib and bevacizumab was feasible with a manageable toxicity profile and demonstrated encouraging efficacy data in a good performance status population.
authors.affiliation: Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: D J
authors.initials: DJ
authors.lastname: Watkins
authors.affiliation: Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Starling
authors.affiliation: Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom. Electronic address: david.cunningham@rmh.nhs.uk.
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Webb
authors.affiliation: Department of Diagnostic Imaging, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Brown
authors.affiliation: Computing and Statistics, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: Y
authors.initials: Y
authors.lastname: Barbachano
authors.affiliation: Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Oates
authors.affiliation: Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: I
authors.initials: I
authors.lastname: Chau
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011799:Quinazolines / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: Anti-angiogenic therapy; Chemotherapy; Combination chemotherapy; Epidermal growth factor receptor (EGFR) inhibition; Molecularly targeted therapy; Pancreatic cancer