A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma

Active specific immunotherapy, using vaccines with autologous tumour cells and BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer patients, while no clinical benefit has yet been observed in stage III patients. Adjuvant treatment with 5-Fluorouracil/Leucovorin is now c...

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Autores principales: Baars, A, Claessen, A M E, Wagstaff, J, Giaccone, G, Scheper, R J, Meijer, S, Schakel, M J A G, Gall, H E, Meijer, C J L M, Vermorken, J B, Pinedo, H M, van den Eertwegh, A J M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2002
Materias:
Clinical
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375342/
https://www.ncbi.nlm.nih.gov/pubmed/11953877
http://dx.doi.org/10.1038/sj.bjc.6600254
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author Baars, A
Claessen, A M E
Wagstaff, J
Giaccone, G
Scheper, R J
Meijer, S
Schakel, M J A G
Gall, H E
Meijer, C J L M
Vermorken, J B
Pinedo, H M
van den Eertwegh, A J M
author_facet Baars, A
Claessen, A M E
Wagstaff, J
Giaccone, G
Scheper, R J
Meijer, S
Schakel, M J A G
Gall, H E
Meijer, C J L M
Vermorken, J B
Pinedo, H M
van den Eertwegh, A J M
author_sort Baars, A
collection PubMed
description Active specific immunotherapy, using vaccines with autologous tumour cells and BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer patients, while no clinical benefit has yet been observed in stage III patients. Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered standard therapy for stage III colon carcinoma and results in an absolute survival benefit of approximately 10%. Yet, the 5-year overall survival rate of stage III colon cancer patients is only 40–50%. Combining chemotherapy and immunotherapy might improve prognosis for stage III patients, especially when considering that active specific immunotherapy and chemotherapy have shown synergistic effects in pre-clinical tumour models. We performed a phase II study with 56 patients, using the combination of active specific immunotherapy and chemotherapy as an adjuvant therapy in stage III colon cancer patients to assess the influence of 5-Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell vaccinations. Anti-tumour immunity was measured before and after chemotherapy by means of delayed type hypersensitivity reactions, taken 48 h after the third and the fourth vaccination. We also investigated the toxicity of this combined immuno-chemotherapy treatment. Delayed type hypersensitivity reactions before chemotherapy had a median size of 20.3 mm, while after chemotherapy delayed type hypersensitivity size was 18.4 mm (P=0.01), indicating that chemotherapy hardly affected anti-tumour immunity. The severity of ulcers at the BCG vaccination sites was comparable to previous studies. In 30% of the patients grade III or grade IV chemotherapy related toxicity was seen; this is comparable to what is normally observed after adjuvant chemotherapy alone. This study shows that the active specific immunotherapy-induced anti-tumour immune response is only minimally impaired by consecutive chemotherapy and that the combined treatment of stage III colon cancer patients with active specific immunotherapy and 5-Fluorouracil/Leucovorin does not cause unexpected toxicity. British Journal of Cancer (2002) 86, 1230–1234. DOI: 10.1038/sj/bjc/6600254 www.bjcancer.com © 2002 Cancer Research UK
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spelling pubmed-23753422009-09-10 A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma Baars, A Claessen, A M E Wagstaff, J Giaccone, G Scheper, R J Meijer, S Schakel, M J A G Gall, H E Meijer, C J L M Vermorken, J B Pinedo, H M van den Eertwegh, A J M Br J Cancer Clinical Active specific immunotherapy, using vaccines with autologous tumour cells and BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer patients, while no clinical benefit has yet been observed in stage III patients. Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered standard therapy for stage III colon carcinoma and results in an absolute survival benefit of approximately 10%. Yet, the 5-year overall survival rate of stage III colon cancer patients is only 40–50%. Combining chemotherapy and immunotherapy might improve prognosis for stage III patients, especially when considering that active specific immunotherapy and chemotherapy have shown synergistic effects in pre-clinical tumour models. We performed a phase II study with 56 patients, using the combination of active specific immunotherapy and chemotherapy as an adjuvant therapy in stage III colon cancer patients to assess the influence of 5-Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell vaccinations. Anti-tumour immunity was measured before and after chemotherapy by means of delayed type hypersensitivity reactions, taken 48 h after the third and the fourth vaccination. We also investigated the toxicity of this combined immuno-chemotherapy treatment. Delayed type hypersensitivity reactions before chemotherapy had a median size of 20.3 mm, while after chemotherapy delayed type hypersensitivity size was 18.4 mm (P=0.01), indicating that chemotherapy hardly affected anti-tumour immunity. The severity of ulcers at the BCG vaccination sites was comparable to previous studies. In 30% of the patients grade III or grade IV chemotherapy related toxicity was seen; this is comparable to what is normally observed after adjuvant chemotherapy alone. This study shows that the active specific immunotherapy-induced anti-tumour immune response is only minimally impaired by consecutive chemotherapy and that the combined treatment of stage III colon cancer patients with active specific immunotherapy and 5-Fluorouracil/Leucovorin does not cause unexpected toxicity. British Journal of Cancer (2002) 86, 1230–1234. DOI: 10.1038/sj/bjc/6600254 www.bjcancer.com © 2002 Cancer Research UK Nature Publishing Group 2002-04-22 /pmc/articles/PMC2375342/ /pubmed/11953877 http://dx.doi.org/10.1038/sj.bjc.6600254 Text en Copyright © 2002 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Clinical
Baars, A
Claessen, A M E
Wagstaff, J
Giaccone, G
Scheper, R J
Meijer, S
Schakel, M J A G
Gall, H E
Meijer, C J L M
Vermorken, J B
Pinedo, H M
van den Eertwegh, A J M
A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma
title A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma
title_full A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma
title_fullStr A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma
title_full_unstemmed A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma
title_short A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma
title_sort phase ii study of active specific immunotherapy and5-fu/leucovorin as adjuvant therapy for stage iii colon carcinoma
topic Clinical
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375342/
https://www.ncbi.nlm.nih.gov/pubmed/11953877
http://dx.doi.org/10.1038/sj.bjc.6600254
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