title: Immunity feedback and clinical outcome in colon cancer patients undergoing chemoimmunotherapy with gemcitabine + FOLFOX followed by subcutaneous granulocyte macrophage colony-stimulating factor and aldesleukin (GOLFIG-1 Trial).
abstract: OBJECTIVE
  GOLFIG chemoimmunotherapy regimen proved to be a safe and very active chemoimmunotherapy regimen in advanced colon cancer patients. We have thus investigated the immunobiological feedback to the treatment and its possible correlation with the clinical outcome of these patients.
  
  
  METHODS
  This clinical and immunologic study involved 46 patients, 27 males and 19 females, enrolled in the GOLFIG-1 phase II trial who received gemcitabine (1,000 mg/m(2) on days 1 and 15), oxaliplatin (85 mg/m(2) on days 2 and 16), levofolinic acid (100 mg/m(2) on days 1, 2, 15, and 16), and 5-fluorouracil (400 mg/m(2) as a bolus, and 800 mg/m(2) as a 24-hour infusion on days 1, 2, 15, and 16) followed by s.c. granulocyte macrophage colony-stimulating factor (100 mug, on days 3-7) and interleukin 2 (0.5 x 10(6) IU twice a day on days 8-14 and 17-29).
  
  
  RESULTS
  The regimen was confirmed to be safe and very active in pretreated patients with metastatic colorectal cancer. A subgroup analysis of these patients revealed a prolonged time to progression and survival in six patients who developed late signs of autoimmunity. A multivariate analysis validated the occurrence of autoimmunity signs as an independent predictor of favorable outcome. A parallel immunologic study detected in the peripheral blood mononuclear cells of these patients a progressive increase in lymphocyte and eosinophil counts, amplification in central memory, a marked depletion of immunosuppressive regulatory T cells, and activation of colon cancer-specific cytotoxic T cells.
  
  
  CONCLUSIONS
  Our results suggest that immunity feedback to GOLFIG regimen and its antitumor activity are tightly correlated.
authors.affiliation: Section of Medical Oncology, Department "Giorgio Segre" of Pharmacology, Rheumatology Unit, Siena University School of Medicine, Siena, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Correale
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
authors.forename: Antonella
authors.initials: A
authors.lastname: Fioravanti
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Del Vecchio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Remondo
authors.forename: Francesco
authors.initials: F
authors.lastname: Montagnani
authors.forename: Maria Saveria
authors.initials: MS
authors.lastname: Rotundo
authors.forename: Chiara
authors.initials: C
authors.lastname: Ginanneschi
authors.forename: Ignazio
authors.initials: I
authors.lastname: Martellucci
authors.forename: Edoardo
authors.initials: E
authors.lastname: Francini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cusi
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Guido
authors.initials: G
authors.lastname: Francini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D007376:Interleukin-2; D009944:Organoplatinum Compounds; D011994:Recombinant Proteins; D003841:Deoxycytidine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C082598:aldesleukin; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine