title: A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with pretreated gastroenteropancreatic well-differentiated endocrine carcinomas.
abstract: Only a few drugs are active in the treatment of well-differentiated endocrine carcinomas (WDEC). We evaluated the combination of the so-called 'de Gramont schedule' and irinotecan in these tumors in a phase II study.
  
  
  METHODS
  20 patients were enrolled in the study. The combination regimen included irinotecan, 180 mg/m(2) on day 1, followed by 200 mg/m(2) folinic acid in a 2-hour infusion, an intravenous 10-min bolus of 400 mg/m(2) 5-fluorouracil (5FU) and finally 600 mg/m(2) 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2. Clinical, biological and morphological parameters were assessed by CT every 8 weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3 cases and other sites in 7 cases. Sixteen patients had previously received chemotherapy, and 6 of them had had two lines of treatment. Six patients had previously been treated with chemoembolization.
  
  
  RESULTS
  The median number of cycles administered was 8. Grade 3-4 neutropenia was observed in 8 patients, and 1 patient experienced febrile neutropenia. There was no toxicity-related death. No complete symptomatic response was observed in 7 evaluable patients; 4 patients had an objective biological response. One patient achieved a morphological objective response, stabilization was observed in 15, but progression occurred in 3 patients. Median survival was 15 months.
  
  
  CONCLUSIONS
  The above-mentioned combination of LV5FU2 + irinotecan does not yield major activity in heavily pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant toxicity was observed.
authors.affiliation: Gastroenterology Unit, Institute Gustave Roussy, Villejuif, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Ducreux
authors.forename: V
authors.initials: V
authors.lastname: Boige
authors.forename: S
authors.initials: S
authors.lastname: Leboulleux
authors.forename: D
authors.initials: D
authors.lastname: Malka
authors.forename: P
authors.initials: P
authors.lastname: Kergoat
authors.forename: C
authors.initials: C
authors.lastname: Dromain
authors.forename: D
authors.initials: D
authors.lastname: Elias
authors.forename: T
authors.initials: T
authors.lastname: de Baere
authors.forename: J C
authors.initials: JC
authors.lastname: Sabourin
authors.forename: P
authors.initials: P
authors.lastname: Duvillard
authors.forename: P
authors.initials: P
authors.lastname: Lasser
authors.forename: M
authors.initials: M
authors.lastname: Schlumberger
authors.forename: E
authors.initials: E
authors.lastname: Baudin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002277:Carcinoma / Q000188:drug therapy*; D004334:Drug Administration Schedule; D019858:Enteroendocrine Cells; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin