title: Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  The combination of vaccines and chemotherapy holds promise for cancer therapy, but the effect of cytotoxic chemotherapy on vaccine-induced antitumor immunity is unknown. This study was conducted to assess the effects of systemic chemotherapy on ALVAC-CEA/B7.1-induced T-cell immunity in patients with metastatic colorectal cancer.
  
  
  METHODS
  Patients with metastatic colorectal cancer were treated with fluorouracil, leucovorin, and irinotecan and were also given ALVAC-CEA/B7.1 vaccine with or without tetanus toxoid adjuvant. Eligible patients were randomized to ALVAC followed by chemotherapy and booster vaccination (group 1), ALVAC and tetanus toxoid followed by chemotherapy (group 2), or chemotherapy alone followed by ALVAC in patients without disease progression (group 3). Humoral immune responses were measured by standard ELISA assay, and carcinoembryonic antigen (CEA)-specific T-cell responses were measured by IFN-gamma enzyme-linked immunospot assay.
  
  
  RESULTS
  One hundred eighteen patients were randomized to receive either ALVAC before and concomitantly with chemotherapy (n = 39), ALVAC with tetanus adjuvant before and concomitantly with chemotherapy (n = 40), or chemotherapy followed by ALVAC (n = 39). Serious adverse events were largely gastrointestinal (n = 30) and hematologic (n = 24). Overall, 42 patients (40.4%) showed objective clinical responses. All patients developed antibody responses against ALVAC, but increased anti-CEA antibody titers were detected in only three patients. Increases in CEA-specific T cells were detected in 50%, 37%, and 30% of patients in groups 1, 2, and 3, respectively. There were no differences in clinical or immune responses between the treatment groups.
  
  
  CONCLUSIONS
  The combination of ALVAC-CEA/B7.1 vaccine and systemic chemotherapy has an acceptable safety profile in patients with metastatic colorectal cancer. Systemic chemotherapy did not affect the generation of CEA-specific T-cell responses following vaccination.
authors.affiliation: Columbia University Medical Center, New York, New York 10032, USA. hlk2003@columbia.edu
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Deepti
authors.initials: D
authors.lastname: Singh
authors.forename: Chris
authors.initials: C
authors.lastname: Garett
authors.forename: Christine
authors.initials: C
authors.lastname: Cripps
authors.forename: Malcolm
authors.initials: M
authors.lastname: Moore
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.forename: Richard
authors.initials: R
authors.lastname: Dalfen
authors.forename: William J
authors.initials: WJ
authors.lastname: Heim
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Maria
authors.initials: M
authors.lastname: Yu
authors.forename: Judy
authors.initials: J
authors.lastname: Caterini
authors.forename: Seunghee
authors.initials: S
authors.lastname: Kim-Schulze
authors.forename: Mark
authors.initials: M
authors.lastname: Debenedette
authors.forename: Danielle
authors.initials: D
authors.lastname: Salha
authors.forename: Thorsten
authors.initials: T
authors.lastname: Vogel
authors.forename: Ileana
authors.initials: I
authors.lastname: Elias
authors.forename: Neil L
authors.initials: NL
authors.lastname: Berinstein
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018122:B7-1 Antigen / Q000737:chemistry*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002272:Carcinoembryonic Antigen / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000378:metabolism; D016896:Treatment Outcome; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: C078788:ALVAC vaccine; D018122:B7-1 Antigen; D002272:Carcinoembryonic Antigen; D014765:Viral Vaccines; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin