title: Gemcitabine, oxaliplatin, and capecitabine (GEMOXEL) compared with gemcitabine alone in metastatic pancreatic cancer: a randomized phase II study.
abstract: BACKGROUND
  Single-agent gemcitabine (GEM) has been considered for many years as the standard first-line treatment for advanced pancreatic cancer. However, recently, several studies reported encouraging activity and good tolerability for some combination regimens. Considering the apparently non-overlapping toxicity and the proved individual efficacy of GEM, oxaliplatin (L-OHP), and capecitabine (CAP), this randomized phase II study compared the activity and safety of the combination GEM, L-OHP, and CAP (GEMOXEL) versus GEM alone, in patients with metastatic pancreatic cancer.
  
  
  METHODS
  The treatment in GEMOXEL arm consisted of GEM 1,000 mg/m(2) as a 30-min intravenous infusion on days 1, 8, 15, 22, L-OHP 100 mg/m(2) i.v. on day 2, and CAP 1,500 mg/m(2)/day in two divided doses on days 1-14, every 21 days (one cycle). In both treatment groups, GEM was administered weekly for seven consecutive weeks followed by 1-week rest for the first 8 weeks, and thereafter, GEM was continued on days 1, 8, 15, every 28 days. Chemotherapy was administered until disease progression or unacceptable toxicity.
  
  
  RESULTS
  Sixty-seven patients were enrolled in the study. Thirty-four were randomly assigned to GEMOXEL and 33 to GEM. At 4 months, disease control rate was 79.4% with GEMOXEL versus 45.4 % with GEM (p = 0.004). The median progression-free survival was 6.8 months (95% CI 5.3-7.3 months) in GEMOXEL arm and 3.7 months (95% CI 2.9-4.7 months) in GEM arm (p < 0.001). The median OS was 11.9 months (95% CI 10.6-12.9 months) in GEMOXEL arm and 7.1 months (95% CI 5.5-9.1 months) in GEM arm (p < 0.001). Hematologic and non-hematologic toxicity was more severe with combination chemotherapy, yet still tolerable. No grade 4 adverse events were observed with either regimen.
  
  
  CONCLUSIONS
  GEMOXEL regimen seemed to be safe and more efficient than the standard therapy with GEM alone in the treatment of metastatic pancreatic cancer.
authors.affiliation: Medical Oncology Unit, University of Siena, Viale Bracci 11, 53100, Siena, Italy, r.petrioli@ao-siena.toscana.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Petrioli
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Roviello
authors.forename: Anna Ida
authors.initials: AI
authors.lastname: Fiaschi
authors.forename: Letizia
authors.initials: L
authors.lastname: Laera
authors.forename: Daniele
authors.initials: D
authors.lastname: Marrelli
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
authors.forename: Edoardo
authors.initials: E
authors.lastname: Francini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine