36675
document
Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer . 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-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 . 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-specific T-cell responses following vaccination .
36676
Intervention_Pharmacological
Combination chemotherapy
36677
Intervention_Pharmacological
ALVAC-CEA/B7.1 vaccine
36678
Intervention_Pharmacological
vaccines
36679
Intervention_Pharmacological
chemotherapy
36680
Intervention_Pharmacological
fluorouracil
36681
Intervention_Pharmacological
leucovorin
36682
Intervention_Pharmacological
irinotecan
36683
Intervention_Pharmacological
ALVAC-CEA/B7.1 vaccine
36684
Intervention_Pharmacological
tetanus toxoid adjuvant
36685
Intervention_Pharmacological
ALVAC
36686
Intervention_Pharmacological
chemotherapy
36687
Intervention_Pharmacological
booster vaccination
36688
Intervention_Pharmacological
ALVAC
36689
Intervention_Pharmacological
tetanus toxoid
36690
Intervention_Pharmacological
chemotherapy
36691
Intervention_Pharmacological
chemotherapy
36692
Intervention_Pharmacological
ALVAC
36693
Intervention_Physical
ELISA assay
36694
Intervention_Physical
IFN-gamma enzyme-linked immunospot assay
36695
Intervention_Pharmacological
ALVAC
36696
Intervention_Pharmacological
chemotherapy
36697
Intervention_Pharmacological
ALVAC
36698
Intervention_Pharmacological
tetanus adjuvant
36699
Intervention_Pharmacological
chemotherapy
36700
Intervention_Pharmacological
chemotherapy
36701
Intervention_Pharmacological
ALVAC
36702
Intervention_Pharmacological
ALVAC-CEA/B7.1 vaccine
36703
Intervention_Pharmacological
chemotherapy
36704
Outcome_Adverse-effects
Serious adverse events
36705
Outcome_Adverse-effects
gastrointestinal
36706
Outcome_Adverse-effects
hematologic
36707
Outcome_Physical
antibody responses against ALVAC
36708
Outcome_Physical
anti-CEA antibody titers
36709
Outcome_Physical
CEA-specific T cells
36710
Outcome_Physical
CEA-specific T-cell responses
36711
Participant_Condition
metastatic colorectal cancer
36712
Participant_Sample-size
One hundred eighteen