Fluorinated pyrimidines

Gottschling, Hubert; Heidelberger, Charles

doi:10.1016/s0022-2836(63)80101-1

Cited by 45 publications

(6 citation statements)

References 22 publications

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“…Trifluridine/tipiracil (TFTD), formerly known as TAS-102, is an antitumor therapy (13,14). It comprises a mixture of two distinct chemicals, trifluridine and tipiracil (TPI), at a molar ratio of 1:0.5.…”

Section: Introductionmentioning

confidence: 99%

Trifluridine/tipiracil increases survival rates in peritoneal dissemination mouse models of human colorectal and gastric cancer

2017

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A number of patients exhibit peritoneal dissemination of gastric or colorectal cancer, which is a predominant cause of cancer-associated mortality. Currently, there is no markedly effective treatment available. The present study was designed to determine the efficacy of trifluridine/tipiracil (TFTD), formerly known as TAS-102, which is used for the treatment of patients with unresectable advanced or recurrent colorectal cancer refractory to standard therapies. Four colorectal cancer cell lines and one gastric cancer cell line were intraperitoneally inoculated into nude mice, as models of peritoneal dissemination. TFTD (200 mg/kg/day) was orally administered for 5 consecutive days followed by 2 drug-free days for 6 weeks. The increase in the lifespan (ILS) of the TFTD-treated mice compared with that of the drug-free control mice was 66.7, 43.3, 106.3, 98.3 and 133.3% for DLD-1, DLD-1/5-fluorouracil [5-fluorouracil (5FU)-resistant subline of DLD-1], HT-29 and HCT116 colorectal cancer cell lines, and MKN45 gastric cancer cell line, respectively. This ILS was similar to that of the irinotecan-treated mice (ILS, 70–84%), but was significantly (P<0.05) increased compared with that of the 5FU-, tegafur, gimeracil and potassium oxonate- and cisplatin-treated mice (ILS, 1–53%, 0.8–60% and 85%, respectively). No significant increase in body weight loss was observed during the dosing periods with any of the drugs used. The increase in CEA levels with progressive peritoneal dissemination was inhibited by TFTD treatment. TFTD also exhibited marked anticancer effects against Kirsten rat sarcoma viral oncogene homolog-mutated tumors and 5FU-resistant tumors. The results of the present study indicate that TFTD may be a potential drug against peritoneal dissemination of colorectal and/or gastric cancer in humans and may be utilized for chemo-naïve tumors and recurrent tumors following 5FU treatment.

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Section: Introductionmentioning

confidence: 99%

Trifluridine/tipiracil increases survival rates in peritoneal dissemination mouse models of human colorectal and gastric cancer

2017

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“…1, IV) (1 3 ) , in which the three hydrogens on the methyl group of thymidine were replaced by fluorine atoms. As expected this compound was incorporated into DNA and not RNA (14). Although it was tried clinically as a tumorinhibitory drug, its effects were not remarkable; however, its antiviral activity against herpes keratitis is highly significant (1 5).…”

Section: Introductionmentioning

confidence: 74%

Fluorinated Pyrimidines and Their Nucleosides

Heidelberger¹,

Danenberg²,

Moran³

1983

Advances in Enzymology - And Related Areas of Molecular Biology

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“… 23 These results reveal that elderly patients can tolerate TAS-102 as well as young patients without frequent interruptions due to adverse events. 24 , 25 The advantage was evident regardless of the presence or absence of mutations in KRAS and BRAF .…”

Section: Discussionmentioning

confidence: 95%

TAS-102 in metastatic colorectal cancer (mCRC): efficacy, tolerability, and quality of life in heavily pretreated elderly patients: a real-life study

Cicero¹,

Addeo²,

Luca³

et al. 2020

DIC

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Background TAS-102 is an oral monotherapy, combining trifluridine and tipiracil hydrochloride, indicated for the treatment of pretreated metastatic colorectal cancer (mCRC). The aim of this real-life study is to evaluate the efficacy and safety of TAS-102 in heavily pretreated elderly patients with mCRC whose disease has progressed with standard therapies. Methods In this retrospective observational study, we enrolled 50 elderly patients >70 years of age (median age 78 years) with a diagnosis of mCRC who were previously treated or were not considered candidates for treatment with other available therapies. Patients aged >70 years with advanced colorectal cancer and with an ECOG performance status of grade 0 ( n =18) or grade 1 ( n =32) were included. Overall survival and progression-free survival were the primary endpoints, whereas objective response rate, tolerability, and quality of life were the secondary endpoints. Results Treatment with TAS-102 appeared to be well tolerated and side effects were generally mild, achieving disease control and a benefit on quality of life. The median overall survival was 6.7 (95% CI 5.7–11.3) and the median progression-free survival was 2.1 months (95% CI 1.2–3.2), estimated using the Kaplan–Meier method. Conclusion TAS-102 represents a manageable and effective therapeutic opportunity and appeared to be well tolerated with generally mild side effects in elderly patients with mCRC who were heavily pretreated with standard therapies.

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Fluorinated pyrimidines

Cited by 45 publications

References 22 publications

Trifluridine/tipiracil increases survival rates in peritoneal dissemination mouse models of human colorectal and gastric cancer

Trifluridine/tipiracil increases survival rates in peritoneal dissemination mouse models of human colorectal and gastric cancer

Fluorinated Pyrimidines and Their Nucleosides

TAS-102 in metastatic colorectal cancer (mCRC): efficacy, tolerability, and quality of life in heavily pretreated elderly patients: a real-life study

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