Combination Chemotherapy and ALVAC-CEA/B7.1 Vaccine in Patients with Metastatic Colorectal Cancer
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- Howard L. Kaufman
- 1Columbia University Medical Center, New York, New York;
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- Heinz-Josef Lenz
- 2Norris Cancer Center, University of Southern California, Los Angeles, California;
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- John Marshall
- 3Georgetown University Medical Center, Washington, District of Columbia;
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- Deepti Singh
- 4University of Chicago;
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- Chris Garett
- 6H. Lee Moffitt Cancer Center, Tampa, Florida;
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- Christine Cripps
- 7Ottawa Regional Cancer Center, Ottawa, Ontario, Canada;
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- Malcolm Moore
- 8Princess Margaret Hospital;
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- Margaret von Mehren
- 10Fox Chase Cancer Center, Philadelphia, Pennsylvania;
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- Richard Dalfen
- 11McGill University, Montreal, Quebec, Canada;
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- William J. Heim
- 12Hematology and Oncology Associates of Northeastern Pennsylvania, Dunmore, Pennsylvania;
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- Robert M. Conry
- 13Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama; and
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- Walter J. Urba
- 14Earle A. Chiles Research Institute, Portland, Oregon
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- Al B. Benson
- 5Northwestern University, Chicago, Illinois;
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- Maria Yu
- 9Sanofi Pasteur, Toronto, Ontario, Canada;
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- Judy Caterini
- 9Sanofi Pasteur, Toronto, Ontario, Canada;
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- Seunghee Kim-Schulze
- 1Columbia University Medical Center, New York, New York;
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- Mark DeBenedette
- 9Sanofi Pasteur, Toronto, Ontario, Canada;
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- Danielle Salha
- 9Sanofi Pasteur, Toronto, Ontario, Canada;
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- Thorsten Vogel
- 9Sanofi Pasteur, Toronto, Ontario, Canada;
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- Ileana Elias
- 9Sanofi Pasteur, Toronto, Ontario, Canada;
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- Neil L. Berinstein
- 9Sanofi Pasteur, Toronto, Ontario, Canada;
抄録
<jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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-γ enzyme-linked immunospot assay.</jats:p><jats:p>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.</jats:p><jats:p>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.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 14 (15), 4843-4849, 2008-08-01
American Association for Cancer Research (AACR)
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キーワード
詳細情報 詳細情報について
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- CRID
- 1361137045491760512
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- ISSN
- 15573265
- 10780432
- http://id.crossref.org/issn/10780432
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- データソース種別
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- Crossref