Pharmacological effects of the simultaneous and sequential combinations of trifluridine/tipiracil (TAS-102) and 5-fluorouracil in fluoropyrimidine-sensitive colon cancer cells.
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Apoptosis
Cell Proliferation
Colonic Neoplasms
/ drug therapy
Drug Combinations
Drug Synergism
Fluorouracil
/ administration & dosage
Humans
Pyrrolidines
/ administration & dosage
Thymine
/ administration & dosage
Trifluridine
/ administration & dosage
Tumor Cells, Cultured
5-fluorouracil
Colon cancer
Proliferation
Synergism
TAS-102
Tipiracil
Trifluridine
Journal
Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
24
04
2019
accepted:
28
05
2019
pubmed:
4
6
2019
medline:
6
10
2020
entrez:
3
6
2019
Statut:
ppublish
Résumé
The aim of this study was to investigate possible synergistic effects in vitro of trifluridine/tipiracil (TAS-102) and 5-fluoruracil (5-FU) on fluoropyrimidine-sensitive colon cancer cell lines of different mutational status in order to build a rational basis for the future use of this combination therapy in adjuvant settings or as a first-line treatment for metastatic disease. Proliferation assays were performed on HT-29 (B-raf mutated), SW-620 (ras mutated), and Caco-2 (wild type) colon cancer cell lines exposed to 120-h treatments of 5-FU, TAS-102 and their different combination schedules (simultaneous, sequential and reverse) at equimolar and non-equimolar ratios. The synergistic, additive and antagonistic effects of 5-FU and TAS-102 were determined by the combination index (CI) and dose reduction index (DRI). Our preclinical in vitro results may suggest an apparently counterintuitive but strongly synergistic combination of 5-FU and TAS-102 in fluoropyrimidine-sensitive colon cancer cells allowing a marked theoretical reduction in the administered doses of both drugs. In particular, this association seems to be highly effective in wild-type colon cancer cells, both in sequential and simultaneous schedules. Together, these data may build a rational basis for the future use of TAS-102 combined with 5-FU in adjuvant settings, or as a first-line treatment for metastatic disease.
Identifiants
pubmed: 31154566
doi: 10.1007/s10637-019-00804-5
pii: 10.1007/s10637-019-00804-5
doi:
Substances chimiques
Drug Combinations
0
Pyrrolidines
0
tipiracil
NGO10K751P
Thymine
QR26YLT7LT
Trifluridine
RMW9V5RW38
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
92-98Références
Sanchez-Gundin J, Fernandez-Carballido AM, Martinez-Valdivieso L, Barreda-Hernandez D, Torres-Suarez AI (2018) New trends in the therapeutic approach to metastatic colorectal cancer. Int J Med Sci 15(7):659–665. https://doi.org/10.7150/ijms.24453
doi: 10.7150/ijms.24453
pubmed: 29910669
pmcid: 6001415
Yee NS (2018) Update in systemic and targeted therapies in gastrointestinal oncology. Biomedicines 6(1). https://doi.org/10.3390/biomedicines6010034
doi: 10.3390/biomedicines6010034
Wu C (2018) Systemic therapy for colon cancer. Surg Oncol Clin N Am 27(2):235–242. https://doi.org/10.1016/j.soc.2017.11.001
doi: 10.1016/j.soc.2017.11.001
pubmed: 29496087
Peeters M, Cervantes A, Moreno Vera S, Taieb J (2018) Trifluridine/tipiracil: an emerging strategy for the management of gastrointestinal cancers. Future Oncol 14(16):1629–1645. https://doi.org/10.2217/fon-2018-0147
doi: 10.2217/fon-2018-0147
pubmed: 29701076
Suzuki N, Nakagawa F, Nukatsuka M, Fukushima M (2011) Trifluorothymidine exhibits potent antitumor activity via the induction of DNA double-strand breaks. Exp Ther Med 2(3):393–397. https://doi.org/10.3892/etm.2011.244
doi: 10.3892/etm.2011.244
pubmed: 22977515
pmcid: 3440718
Temmink OH, Bijnsdorp IV, Prins HJ, Losekoot N, Adema AD, Smid K, Honeywell RJ, Ylstra B, Eijk PP, Fukushima M, Peters GJ (2010) Trifluorothymidine resistance is associated with decreased thymidine kinase and equilibrative nucleoside transporter expression or increased secretory phospholipase A2. Mol Cancer Ther 9(4):1047–1057. https://doi.org/10.1158/1535-7163.mct-09-0932
doi: 10.1158/1535-7163.mct-09-0932
pubmed: 20371715
Marcus L, Lemery SJ, Khasar S, Wearne E, Helms WS, Yuan W, He K, Cao X, Yu J, Zhao H, Wang Y, Stephens O, Englund E, Agarwal R, Keegan P, Pazdur R (2017) FDA approval summary: TAS-102. Clin Cancer Res 23(12):2924–2927. https://doi.org/10.1158/1078-0432.ccr-16-2157
doi: 10.1158/1078-0432.ccr-16-2157
pubmed: 28213365
Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5):330–338. https://doi.org/10.1038/nrc1074
doi: 10.1038/nrc1074
pubmed: 12724731
Matsuoka K, Iimori M, Niimi S, Tsukihara H, Watanabe S, Kiyonari S, Kiniwa M, Ando K, Tokunaga E, Saeki H, Oki E, Maehara Y, Kitao H (2015) Trifluridine induces p53-dependent sustained G2 phase arrest with its massive misincorporation into dna and few dna strand breaks. Mol Cancer Ther 14(4):1004–1013. https://doi.org/10.1158/1535-7163.mct-14-0236
doi: 10.1158/1535-7163.mct-14-0236
pubmed: 25700705
Baba T, Kokuryo T, Yamaguchi J, Yokoyama Y, Uehara K, Ebata T, Nagino M (2018) Pre-exposure to fluorouracil increased Trifluridine incorporation and enhanced its anti-tumor effect for colorectal cancer. Anticancer Res 38(3):1427–1434. https://doi.org/10.21873/anticanres.12367
doi: 10.21873/anticanres.12367
pubmed: 29491068
Brunetti I, Falcone A, Calabresi P, Goulette FA, Darnowski JW (1990) 5-fluorouracil enhances azidothymidine cytotoxicity: in vitro, in vivo, and biochemical studies. Cancer Res 50(13):4026–4031
pubmed: 2354452
Andreuccetti M, Allegrini G, Antonuzzo A, Malvaldi G, Conte PF, Danesi R, Del Tacca M, Falcone A (1996) Azidothymidine in combination with 5-fluorouracil in human colorectal cell lines: in vitro synergistic cytotoxicity and DNA-induced strand-breaks. Eur J Cancer 32A (7):1219–1226
doi: 10.1016/0959-8049(96)00018-4
Chou TC (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58(3):621–681. https://doi.org/10.1124/pr.58.3.10
doi: 10.1124/pr.58.3.10
pubmed: 16968952
Patel AK, Duh MS, Barghout V, Yenikomshian MA, Xiao Y, Wynant W, Tabesh M, Fuchs CS (2018) Real-world treatment patterns among patients with colorectal cancer treated with Trifluridine/Tipiracil and Regorafenib. Clin Colorectal Cancer 17(3):e531–e539. https://doi.org/10.1016/j.clcc.2018.04.002
doi: 10.1016/j.clcc.2018.04.002
pubmed: 29803544
Mulet N, Matos I, Noguerido A, Martini G, Elez ME, Argiles G, Tabernero J (2018) Evaluating trifluridine + tipiracil hydrochloride in a fixed combination (TAS-102) for the treatment of colorectal cancer. Expert Opin Pharmacother 19(6):623–629. https://doi.org/10.1080/14656566.2018.1453497
doi: 10.1080/14656566.2018.1453497
pubmed: 29537896
Temmink OH, Hoogeland MF, Fukushima M, Peters GJ (2006) Low folate conditions may enhance the interaction of trifluorothymidine with antifolates in colon cancer cells. Cancer Chemother Pharmacol 57(2):171–179. https://doi.org/10.1007/s00280-005-0033-4
doi: 10.1007/s00280-005-0033-4
pubmed: 16010590
Matsuoka K, Nakagawa F, Tanaka N, Okabe H, Matsuo K, Takechi T (2018) Effective sequential combined chemotherapy with Trifluridine/Tipiracil and regorafenib in human colorectal cancer cells. Int J Mol Sci 19(10). https://doi.org/10.3390/ijms19102915
doi: 10.3390/ijms19102915
Matsuoka K, Takechi T (2017) Combined efficacy and mechanism of trifluridine and SN-38 in a 5-FU-resistant human colorectal cancer cell lines. Am J Cancer Res 7(12):2577–2586
pubmed: 29312810
pmcid: 5752697
Suzuki N, Tsukihara H, Nakagawa F, Kobunai T, Takechi T (2017) Synergistic anticancer activity of a novel oral chemotherapeutic agent containing trifluridine and tipiracil in combination with anti-PD-1 blockade in microsatellite stable-type murine colorectal cancer cells. Am J Cancer Res 7(10):2032–2040
pubmed: 29119052
pmcid: 5665850
Gong J, Chen Y, Yang L, Pillai R, Shirasawa S, Fakih M (2017) MEK162 enhances antitumor activity of 5-fluorouracil and Trifluridine in KRAS-mutated human colorectal cancer cell lines. Anticancer Res 37(6):2831–2838. https://doi.org/10.21873/anticanres.11634
doi: 10.21873/anticanres.11634
pubmed: 28551618