title: Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed by secondary metastatic resection after downsizing.
abstract: BACKGROUND
  The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV).
  
  
  METHODS
  From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m²) as 1-h infusion followed by 5-FU (2000 mg/m²) combined with FA (500 mg/m²) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57).
  
  
  RESULTS
  Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months.
  
  
  CONCLUSIONS
  Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).
authors.affiliation: Department of Internal Medicine 1 of Erlangen University, Erlangen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Koucky
authors.forename: Axel
authors.initials: A
authors.lastname: Wein
authors.forename: Peter C
authors.initials: PC
authors.lastname: Konturek
authors.forename: Heinz
authors.initials: H
authors.lastname: Albrecht
authors.forename: Udo
authors.initials: U
authors.lastname: Reulbach
authors.forename: Gudrun
authors.initials: G
authors.lastname: Männlein
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolff
authors.forename: Nicola
authors.initials: N
authors.lastname: Ostermeier
authors.forename: Dagmar
authors.initials: D
authors.lastname: Busse
authors.forename: Henriette
authors.initials: H
authors.lastname: Golcher
authors.forename: Claus
authors.initials: C
authors.lastname: Schildberg
authors.forename: Rolf
authors.initials: R
authors.lastname: Janka
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.forename: Eckhart G
authors.initials: EG
authors.lastname: Hahn
authors.forename: Jürgen
authors.initials: J
authors.lastname: Siebler
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.forename: Frank
authors.initials: F
authors.lastname: Boxberger
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary* / Q000601:surgery; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011379:Prognosis; D011877:Radionuclide Imaging; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin