Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer

G Chong, A Bhatnagar, D Cunningham, T M Cosgriff, P G Harper, W Steward, J Bridgewater, M Moore, Jamie Cassidy, R Coleman, F Coxon, C H Redfern, J J Jones, R Hawkins, D Northfelt, S Sreedharan, F Valone, J Carmichael

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Background: The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen (CEA). It therefore has the potential, via the anti-idiotypic network, to stimulate immune responses to CEA that may benefit colorectal cancer patients.

    Patients and methods: A total of 630 patients with previously untreated metastatic colorectal cancer were randomised in a 2:1 fashion to receive bolus 5-fluorouracil (5-FU) and leucovorin (LV) plus either 3H1 (n = 422) or placebo (n = 208).

    Results: The addition of 3H1 to 5-FU and LV did not result in increased toxicity. Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm (P = 0.80). Anti-CEA antibody responses were observed in 70% of patients treated with 3H1. Patients with a negative CEA response had a median survival of 8.3 months (95% CI 7.5-11.0) compared with patients with a strong response: median survival not reached (P < 0.001).

    Conclusion: 3H1 is safe and effectively induces immune responses to CEA. Addition of 3H1 to 5-FU and LV was not shown to improve overall patient outcomes. However, improved survival in patients developing anti-CEA responses to 3H1 are provocative and should be studied in further clinical trials.

    Original languageEnglish
    Pages (from-to)437-442
    Number of pages6
    JournalAnnals of Oncology
    Volume17
    DOIs
    Publication statusPublished - 2006

    Keywords

    • anti-idiotype
    • antibody
    • carcinoembryonic antigen
    • response
    • colorectal
    • HUMAN CARCINOEMBRYONIC ANTIGEN
    • IMMUNE-RESPONSES
    • MELANOMA
    • VACCINE
    • MIMICS

    Cite this

    Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer. / Chong, G ; Bhatnagar, A ; Cunningham, D ; Cosgriff, T M ; Harper, P G ; Steward, W ; Bridgewater, J ; Moore, M ; Cassidy, Jamie; Coleman, R ; Coxon, F ; Redfern, C H ; Jones, J J ; Hawkins, R ; Northfelt, D ; Sreedharan, S ; Valone, F ; Carmichael, J .

    In: Annals of Oncology, Vol. 17, 2006, p. 437-442.

    Research output: Contribution to journalArticle

    Chong, G, Bhatnagar, A, Cunningham, D, Cosgriff, TM, Harper, PG, Steward, W, Bridgewater, J, Moore, M, Cassidy, J, Coleman, R, Coxon, F, Redfern, CH, Jones, JJ, Hawkins, R, Northfelt, D, Sreedharan, S, Valone, F & Carmichael, J 2006, 'Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer', Annals of Oncology, vol. 17, pp. 437-442. https://doi.org/10.1093/annonc/mdj090
    Chong, G ; Bhatnagar, A ; Cunningham, D ; Cosgriff, T M ; Harper, P G ; Steward, W ; Bridgewater, J ; Moore, M ; Cassidy, Jamie ; Coleman, R ; Coxon, F ; Redfern, C H ; Jones, J J ; Hawkins, R ; Northfelt, D ; Sreedharan, S ; Valone, F ; Carmichael, J . / Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer. In: Annals of Oncology. 2006 ; Vol. 17. pp. 437-442.
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    title = "Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer",
    abstract = "Background: The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen (CEA). It therefore has the potential, via the anti-idiotypic network, to stimulate immune responses to CEA that may benefit colorectal cancer patients.Patients and methods: A total of 630 patients with previously untreated metastatic colorectal cancer were randomised in a 2:1 fashion to receive bolus 5-fluorouracil (5-FU) and leucovorin (LV) plus either 3H1 (n = 422) or placebo (n = 208).Results: The addition of 3H1 to 5-FU and LV did not result in increased toxicity. Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm (P = 0.80). Anti-CEA antibody responses were observed in 70{\%} of patients treated with 3H1. Patients with a negative CEA response had a median survival of 8.3 months (95{\%} CI 7.5-11.0) compared with patients with a strong response: median survival not reached (P < 0.001).Conclusion: 3H1 is safe and effectively induces immune responses to CEA. Addition of 3H1 to 5-FU and LV was not shown to improve overall patient outcomes. However, improved survival in patients developing anti-CEA responses to 3H1 are provocative and should be studied in further clinical trials.",
    keywords = "anti-idiotype, antibody, carcinoembryonic antigen, response, colorectal, HUMAN CARCINOEMBRYONIC ANTIGEN, IMMUNE-RESPONSES, MELANOMA, VACCINE, MIMICS",
    author = "G Chong and A Bhatnagar and D Cunningham and Cosgriff, {T M} and Harper, {P G} and W Steward and J Bridgewater and M Moore and Jamie Cassidy and R Coleman and F Coxon and Redfern, {C H} and Jones, {J J} and R Hawkins and D Northfelt and S Sreedharan and F Valone and J Carmichael",
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    TY - JOUR

    T1 - Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer

    AU - Chong, G

    AU - Bhatnagar, A

    AU - Cunningham, D

    AU - Cosgriff, T M

    AU - Harper, P G

    AU - Steward, W

    AU - Bridgewater, J

    AU - Moore, M

    AU - Cassidy, Jamie

    AU - Coleman, R

    AU - Coxon, F

    AU - Redfern, C H

    AU - Jones, J J

    AU - Hawkins, R

    AU - Northfelt, D

    AU - Sreedharan, S

    AU - Valone, F

    AU - Carmichael, J

    PY - 2006

    Y1 - 2006

    N2 - Background: The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen (CEA). It therefore has the potential, via the anti-idiotypic network, to stimulate immune responses to CEA that may benefit colorectal cancer patients.Patients and methods: A total of 630 patients with previously untreated metastatic colorectal cancer were randomised in a 2:1 fashion to receive bolus 5-fluorouracil (5-FU) and leucovorin (LV) plus either 3H1 (n = 422) or placebo (n = 208).Results: The addition of 3H1 to 5-FU and LV did not result in increased toxicity. Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm (P = 0.80). Anti-CEA antibody responses were observed in 70% of patients treated with 3H1. Patients with a negative CEA response had a median survival of 8.3 months (95% CI 7.5-11.0) compared with patients with a strong response: median survival not reached (P < 0.001).Conclusion: 3H1 is safe and effectively induces immune responses to CEA. Addition of 3H1 to 5-FU and LV was not shown to improve overall patient outcomes. However, improved survival in patients developing anti-CEA responses to 3H1 are provocative and should be studied in further clinical trials.

    AB - Background: The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen (CEA). It therefore has the potential, via the anti-idiotypic network, to stimulate immune responses to CEA that may benefit colorectal cancer patients.Patients and methods: A total of 630 patients with previously untreated metastatic colorectal cancer were randomised in a 2:1 fashion to receive bolus 5-fluorouracil (5-FU) and leucovorin (LV) plus either 3H1 (n = 422) or placebo (n = 208).Results: The addition of 3H1 to 5-FU and LV did not result in increased toxicity. Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm (P = 0.80). Anti-CEA antibody responses were observed in 70% of patients treated with 3H1. Patients with a negative CEA response had a median survival of 8.3 months (95% CI 7.5-11.0) compared with patients with a strong response: median survival not reached (P < 0.001).Conclusion: 3H1 is safe and effectively induces immune responses to CEA. Addition of 3H1 to 5-FU and LV was not shown to improve overall patient outcomes. However, improved survival in patients developing anti-CEA responses to 3H1 are provocative and should be studied in further clinical trials.

    KW - anti-idiotype

    KW - antibody

    KW - carcinoembryonic antigen

    KW - response

    KW - colorectal

    KW - HUMAN CARCINOEMBRYONIC ANTIGEN

    KW - IMMUNE-RESPONSES

    KW - MELANOMA

    KW - VACCINE

    KW - MIMICS

    U2 - 10.1093/annonc/mdj090

    DO - 10.1093/annonc/mdj090

    M3 - Article

    VL - 17

    SP - 437

    EP - 442

    JO - Annals of Oncology

    JF - Annals of Oncology

    SN - 0923-7534

    ER -