TY - JOUR
T1 - Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer
AU - Kaufman, Howard L.
AU - Lenz, Heinz Josef
AU - Marshall, John
AU - Singh, Deepti
AU - Garett, Chris
AU - Cripps, Christine
AU - Moore, Malcolm
AU - Von Mehren, Margaret
AU - Dalfen, Richard
AU - Heim, William J.
AU - Conry, Robert M.
AU - Urba, Walter J.
AU - Benson, Al B.
AU - Yu, Maria
AU - Caterini, Judy
AU - Kim-Schulze, Seunghee
AU - DeBenedette, Mark
AU - Salha, Danielle
AU - Vogel, Thorsten
AU - Elias, Ileana
AU - Berinstein, Neil L.
PY - 2008/8/1
Y1 - 2008/8/1
N2 - Purpose: 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. Experimental Design: 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-7 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 Tcells 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. Conclusion: 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-specificT-cell responses following vaccination.
AB - Purpose: 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. Experimental Design: 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-7 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 Tcells 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. Conclusion: 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-specificT-cell responses following vaccination.
UR - http://www.scopus.com/inward/record.url?scp=51049083164&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-0276
DO - 10.1158/1078-0432.CCR-08-0276
M3 - Article
C2 - 18676757
AN - SCOPUS:51049083164
SN - 1078-0432
VL - 14
SP - 4843
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -