title: A phase II study of sorafenib, oxaliplatin, and 2 days of high-dose capecitabine in advanced pancreas cancer.
abstract: OBJECTIVE
  Fluoropyrimidines and oxaliplatin have demonstrated some efficacy against pancreatic adenocarcinoma, but survival remains brief. Sorafenib is an oral multikinase inhibitor which we sought to combine with a unique capecitabine and oxaliplatin regimen for pancreatic adenocarcinoma.
  
  
  METHODS
  We performed a multicenter phase II study of sorafenib 200 mg orally twice daily along with oxaliplatin 85 mg/m(2) IV on days 1 and 15, followed by capecitabine 2250 mg/m(2) orally every 8 h for six doses starting on days 1 and 15 of a 28-day cycle in patients who had no more than one previous chemotherapy regimen for their pancreatic adenocarcinoma. The primary objective was response rate; secondary objectives were progression-free survival (PFS), overall survival (OS), and safety.
  
  
  RESULTS
  Twenty-four patients were enrolled; median age was 63 years (range 48-83). The most common related toxicities were fatigue, neuropathy, anemia, thrombocytopenia, diarrhea, nausea, leukopenia, and hand-foot syndrome. Grade 3 hand-foot syndrome was rare (4 %). Other grade 4 toxicities included abdominal pain (8 %), pulmonary embolism (4 %), and anemia (4 %). Three partial responses were seen (13 %), and 11 patients had stable disease (46 %) as their best response. Median PFS was 6.0 months (range 1.5-13 months). Median OS was 8.1 months (range 1.5-13.6 months).
  
  
  CONCLUSIONS
  Sorafenib, oxaliplatin, and capecitabine produced partial responses in patients with advanced pancreatic cancer including previously treated patients and demonstrated a PFS of 6 months with few grade 3/4 toxicities.
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, rmakielski@uwhealth.org.
authors.forename: Rory J
authors.initials: RJ
authors.lastname: Makielski
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Lubner
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mulkerin
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.forename: David
authors.initials: D
authors.lastname: Groteluschen
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.forename: Noelle K
authors.initials: NK
authors.lastname: LoConte
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D000077157:Sorafenib
chemical_list: D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D011725:Pyridines; C431073:oxiplatin; D003841:Deoxycytidine; D009536:Niacinamide; D000069287:Capecitabine; D000077157:Sorafenib; D005472:Fluorouracil