title: A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan.
abstract: BACKGROUND
  The G17DT is a novel human immunogen that raises antibodies to the growth factor gastrin 17 (G17). The purpose of this study was to determine the safety and efficacy of G17DT in combination with irinotecan in patients refractory to irinotecan, and to correlate efficacy with anti-G17 immune response.
  
  
  METHODS
  Patients received G17DT immunogen as a single intramuscular injection of 500 μg at weeks 1, 5, 9, and 26. Irinotecan was administered as an intravenous infusion of 125 mg/m(2) over 90 min starting at week 5. Each cycle of treatment consisted of irinotecan administered once weekly for 4 weeks, followed by a 2-week rest period.
  
  
  RESULTS
  Of 161 patients who received G17DT, the best overall tumor response in the intent-to-treat population was complete response 0 (0 %), partial response 3 (3 %), stable disease 32 (32 %), and progressive disease 64 (65 %). Median survival was 217 days. About 94 (62 %) subjects evaluable for antibody titers were anti-G17 responders. Survival was significantly longer for anti-G17 responders compared with non-responders (9.0 vs. 5.6 months; P < 0.001). Toxicity was consistent with irinotecan (diarrhea, nausea, anemia, vomiting, fatigue, constipation, anorexia, and neutropenia) except for injection site reactions (pain 42 %, induration 13 %, edema 11 %, erythema 10 %, and three abscesses) attributed to G17DT in 52 % of the patients.
  
  
  CONCLUSIONS
  Treatment with G17DT in combination with irinotecan results in an acceptable anti-G17 immune response, which correlated with promising survival activity in patients refractory to irinotecan-based chemotherapy.
authors.affiliation: Sylvester Comprehensive Cancer Center, Divisions of Hematology/Oncology, School of Medicine, University of Miami Miller, 1475 NW 12th Ave St 3300, Miami, FL, 33136, USA, crocha@med.miami.edu.
authors.forename: Caio Max
authors.initials: CM
authors.lastname: Rocha-Lima
authors.forename: Eriberto
authors.initials: E
authors.lastname: de Queiroz Marques Junior
authors.forename: Soley
authors.initials: S
authors.lastname: Bayraktar
authors.forename: Paul
authors.initials: P
authors.lastname: Broome
authors.forename: Charles
authors.initials: C
authors.lastname: Weissman
authors.forename: Marek
authors.initials: M
authors.lastname: Nowacki
authors.forename: Martin
authors.initials: M
authors.lastname: Leslie
authors.forename: Shabbir
authors.initials: S
authors.lastname: Susnerwala
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005755:Gastrins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D019496:Cancer Vaccines; D005755:Gastrins; C482698:gastrin immunogen; D000077146:Irinotecan; D002166:Camptothecin