title: Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal cancer: a pilot study.
abstract: OBJECTIVE
  To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma.
  
  
  METHODS
  We initiated a regimen with at day 1 an injection (iv) of bevacizumab at 5 mg/kg, followed by 180 mg/m(2) irinotecan, followed by Leucovorin 400 mg/m(2), followed by a 5-Fluorouracil bolus 400 mg/m(2); and a 46-h infusion 2400 mg/m(2). Sirolimus was given orally as continuous administration of 2 mg twice a day every days. This treatment was repeated every 14 d.
  
  
  RESULTS
  A total of 12 patients were enrolled. All patients presented with metastatic disease that had failed at least three lines of chemotherapy that contained oxaliplatin, irinotecan and bevacizumab. Cetuximab failure was also observed in all K-Ras wild-type patients. The median number of cycles was 8.5 (range 2-20) and clinical benefit was observed in eight patients. The median time to progression was 5 mo and the median survival was 8 mo. Grade 3 neutropenia developed in four patients, and grade 3 diarrhea and stomatitis in two.
  
  
  CONCLUSIONS
  The combination regimen of 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in advanced colorectal carcinoma after failure of classical treatment is feasible and promising. Further evaluation of this combination is required.
authors.affiliation: Department of Medical Oncology, Georges-Francois Leclerc Cancer Center, INSERM avenir 866, Dijon 21000, France. fghiringhelli@dijon.fnclcc.fr
authors.forename: Francois
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Boris
authors.initials: B
authors.lastname: Guiu
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D005472:Fluorouracil; D020123:Sirolimus; D002166:Camptothecin