Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer.
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.
Kaufman
Howard L
HL
Columbia University Medical Center, New York, New York 10032, USA. hlk2003@columbia.edu
Lenz
Heinz-Josef
HJ
Marshall
John
J
Singh
Deepti
D
Garett
Chris
C
Cripps
Christine
C
Moore
Malcolm
M
von Mehren
Margaret
M
Dalfen
Richard
R
Heim
William J
WJ
Conry
Robert M
RM
Urba
Walter J
WJ
Benson
Al B
AB
Yu
Maria
M
Caterini
Judy
J
Kim-Schulze
Seunghee
S
Debenedette
Mark
M
Salha
Danielle
D
Vogel
Thorsten
T
Elias
Ileana
I
Berinstein
Neil L
NL
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*
C078788:ALVAC vaccine; D018122:B7-1 Antigen; D002272:Carcinoembryonic Antigen; D014765:Viral Vaccines; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin