Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays

Kai Rothkamm; Sabrina Christiansen; Thorsten Rieckmann; Michael Horn; Thorsten Frenzel; Alexandra Brinker; Udo Schumacher; Alexander Stein; Cordula Petersen; Susanne Burdak-Rothkamm

doi:10.1016/j.canlet.2020.08.038

Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays

Standard

Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays. / Rothkamm, Kai; Christiansen, Sabrina; Rieckmann, Thorsten; Horn, Michael; Frenzel, Thorsten; Brinker, Alexandra; Schumacher, Udo ; Stein, Alexander ; Petersen, Cordula ; Burdak-Rothkamm, Susanne.

in: CANCER LETT, Jahrgang 493, 28.11.2020, S. 179-188.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rothkamm, K, Christiansen, S, Rieckmann, T, Horn, M, Frenzel, T, Brinker, A, Schumacher, U , Stein, A , Petersen, C & Burdak-Rothkamm, S 2020, 'Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays', CANCER LETT, Jg. 493, S. 179-188. https://doi.org/10.1016/j.canlet.2020.08.038

APA

Rothkamm, K., Christiansen, S., Rieckmann, T., Horn, M., Frenzel, T., Brinker, A., Schumacher, U., Stein, A., Petersen, C., & Burdak-Rothkamm, S. (2020). Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays. CANCER LETT, 493, 179-188. https://doi.org/10.1016/j.canlet.2020.08.038

Vancouver

Rothkamm K, Christiansen S, Rieckmann T, Horn M, Frenzel T, Brinker A et al. Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays. CANCER LETT. 2020 Nov 28;493:179-188. https://doi.org/10.1016/j.canlet.2020.08.038

Bibtex

@article{62f265537b1c4b1ea2a04154dcce1852,

title = "Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays",

abstract = "Trifluridine/tipiracil (FTD/TPI; marketed as Lonsurf{\textregistered}) has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation. Here we investigated the colorectal cancer cell lines HT29, HCT116, SW48 and Caco-2 to provide a preclinical rationale for FTD/TPI-based chemoradiation treatment. All lines incorporated similar amounts of FTD, irrespective of treatment concentration and duration, then arrested in S phase, showed persistent γH2AX induction and eventually underwent endoreplication, resulting in polyploidy. Clonogenic assays performed for four combined treatment schedules demonstrated additivity for treatments given within 6 h of each other. However, 24 h FTD/TPI treatment prior to irradiation caused 1.6-2.4 fold radiosensitisation. Combined in vivo treatment was well tolerated and caused a marked tumour growth delay, similar to capecitabine radiochemotherapy regimes. Prolonged S phase arrest, persistent γH2AX signalling, endoreplication and polyploidy may contribute to the cytotoxicity of FTD/TPI. The strong radiosensitising effect observed in vitro after prolonged treatment with FTD/TPI and equivalence with capecitabine-based chemoradiation in vivo support a daily fractionated combined regime of FTD/TPI and radiation in rectal cancer treatment. This is now being tested in a phase I/II clinical trial (NCT04177602).",

author = "Kai Rothkamm and Sabrina Christiansen and Thorsten Rieckmann and Michael Horn and Thorsten Frenzel and Alexandra Brinker and Udo Schumacher and Alexander Stein and Cordula Petersen and Susanne Burdak-Rothkamm",

year = "2020",

month = nov,

day = "28",

doi = "10.1016/j.canlet.2020.08.038",

language = "English",

volume = "493",

pages = "179--188",

journal = "CANCER LETT",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays

AU - Rothkamm, Kai

AU - Christiansen, Sabrina

AU - Rieckmann, Thorsten

AU - Horn, Michael

AU - Frenzel, Thorsten

AU - Brinker, Alexandra

AU - Schumacher, Udo

AU - Stein, Alexander

AU - Petersen, Cordula

AU - Burdak-Rothkamm, Susanne

PY - 2020/11/28

Y1 - 2020/11/28

N2 - Trifluridine/tipiracil (FTD/TPI; marketed as Lonsurf®) has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation. Here we investigated the colorectal cancer cell lines HT29, HCT116, SW48 and Caco-2 to provide a preclinical rationale for FTD/TPI-based chemoradiation treatment. All lines incorporated similar amounts of FTD, irrespective of treatment concentration and duration, then arrested in S phase, showed persistent γH2AX induction and eventually underwent endoreplication, resulting in polyploidy. Clonogenic assays performed for four combined treatment schedules demonstrated additivity for treatments given within 6 h of each other. However, 24 h FTD/TPI treatment prior to irradiation caused 1.6-2.4 fold radiosensitisation. Combined in vivo treatment was well tolerated and caused a marked tumour growth delay, similar to capecitabine radiochemotherapy regimes. Prolonged S phase arrest, persistent γH2AX signalling, endoreplication and polyploidy may contribute to the cytotoxicity of FTD/TPI. The strong radiosensitising effect observed in vitro after prolonged treatment with FTD/TPI and equivalence with capecitabine-based chemoradiation in vivo support a daily fractionated combined regime of FTD/TPI and radiation in rectal cancer treatment. This is now being tested in a phase I/II clinical trial (NCT04177602).

AB - Trifluridine/tipiracil (FTD/TPI; marketed as Lonsurf®) has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation. Here we investigated the colorectal cancer cell lines HT29, HCT116, SW48 and Caco-2 to provide a preclinical rationale for FTD/TPI-based chemoradiation treatment. All lines incorporated similar amounts of FTD, irrespective of treatment concentration and duration, then arrested in S phase, showed persistent γH2AX induction and eventually underwent endoreplication, resulting in polyploidy. Clonogenic assays performed for four combined treatment schedules demonstrated additivity for treatments given within 6 h of each other. However, 24 h FTD/TPI treatment prior to irradiation caused 1.6-2.4 fold radiosensitisation. Combined in vivo treatment was well tolerated and caused a marked tumour growth delay, similar to capecitabine radiochemotherapy regimes. Prolonged S phase arrest, persistent γH2AX signalling, endoreplication and polyploidy may contribute to the cytotoxicity of FTD/TPI. The strong radiosensitising effect observed in vitro after prolonged treatment with FTD/TPI and equivalence with capecitabine-based chemoradiation in vivo support a daily fractionated combined regime of FTD/TPI and radiation in rectal cancer treatment. This is now being tested in a phase I/II clinical trial (NCT04177602).

U2 - 10.1016/j.canlet.2020.08.038

DO - 10.1016/j.canlet.2020.08.038

M3 - SCORING: Journal article

C2 - 32891715

VL - 493

SP - 179

EP - 188

JO - CANCER LETT

JF - CANCER LETT

SN - 0304-3835

ER -