Tegafur Research Articles

Effect of apatinib combined with tegafur, gimeracil and oteracil potassium on advanced gastric cancer

目的 探讨阿帕替尼联合替吉奥治疗晚期胃癌的有效性和安全性。 方法 选择2015年1月至2016年12月福建医科大学附属协和医院收治的晚期胃癌患者28例，采用阿帕替尼联合替吉奥治疗，观察其有效率并评价不良反应。 结果 28例患者均可评价疗效，总体有效率为32.1%（9/28），疾病控制率为60.7%（17/28）；其中一线治疗患者有效率为44.4%（4/9），疾病控制率为88.9%（8/9）；非一线（二线、三线及以上）患者有效率为26.3%（5/19），疾病控制率为47.4%（9/19）；主要的不良反应为白细胞减少、血小板减少、高血压、蛋白尿等，大多为Ⅰ~Ⅱ度，Ⅲ~Ⅳ度少见。 结论 晚期胃癌患者应用阿帕替尼联合替吉奥治疗的近期疗效理想，不良反应轻，可应用于不能耐受常规联合化疗或不愿接受静脉化疗的患者。

Comparison of efficacy of Oxaliplatin combined with Tegafur Gimeracil Oteracil Potassium Capsule and mFOLFOX6 method in the treatment of gastric cancer with liver metastasis

Objective To compare the efficacy and influence on the immune function of oxaliplatin combined with tegafur gimeracil oteracil potassium capsule and mFOLFOX6 method in the treatment of gastric cancer with liver metastasis. Methods One hundred and thirty-four gastric cancer with liver metastasis patients who underwent treatment from Jan. 2014 to Jan. 2016 in Yulin First Hospital were selected as the participants and randomly divided observation group (67 cases) and control group (67 cases). The control group was treated by mFOLFOX6 method, while the observation group was treated by oxaliplatin combined with tegafur gimeracil oteracil potassium capsule. After treatment, the curative effects were evaluated. The life quality in each group as performed by KPS method before the treatment and in every period of treatment. Before and after the treatment, the levels of CD3+ , CD4+ , CD8+ and CD19+ were detected in two groups and the toxicity was compared. The SPSS 22.0 software was used to analyze relevant data, the measurement data was described by (±s) and using t-test, the enumeration data was described by percentage, using the Chi-square test. Results The total effective rate was 52.2% in the observation group, higher than the 38.8% in the control group (P<0.05). After the third and fourth course of treatment, the karnofsky perfomance status score were (81.3±9.7) and (83.2±9.9), were significantly higher in the observation group than which in the control group (P< 0.05). After the treatment, the levels of CD3+ , CD4+ , CD8+ and CD19+ were (54.21±6.38)%, (24.11±2.41) %, (21.33±3.16) % and (7.18±1.13) % in the observation group, and higher than the control group (P< 0.05). During the treatment, there were no serious toxicity occurs in the patients and the rates of toxicity were significantly lower in the observation group than which in the control group (P< 0.05). Conclusion Oxaliplatin combined with tegafur gimeracil oteracil potassium capsule has a better effect and safety for therapy in the treatment of gastric cancer with liver metastasis than mFOLFOX6. Key words: mFOLFOX6 method; Oxaliplatin; Tegafur gimeracil oteracil potassium capsule; Stomach neoplasms; Liver metastasis; Comparative effectiveness research; Chi-square distribution

Observation of the effect of hyperthermia combined with chemotherapy in patients with advanced gastric carcinoma

Objective To observe the therapeutic efficacy and security of hyperthermia combined with chemotherapy for advanced gastric carcinoma. Methods The clinical data of 126 patients with advanced gastric cancer were retrospectively analyzed.According to the different treatment methods, they were divided into simple chemotherapy group(A group, 63 cases) and chemotherapy combined with hyperthermia group (B group, 63 cases). A group received chemotherapy through vein, the patients received docetaxel 75mg/m2 on day 1, tegafur 80mg/m2 on day 1-14 and cisplatin 75mg/m2 on day 2-4 of 21-day courses.B group received hyperthermia together with chemotherapy.Hyperthermia was maintained at 40-42℃ for 90min.The efficacy and toxicity-side-effect after the patients received two courses were evaluated. Results In A group, the rate of complete remission(CR) was 0 case, partial remission(PR) in 28 cases, stable disease(SD) in 27 cases, progressive disease(PD) in 8 cases, and the overall response rate(CR+ PR) was 44.4%, while those in B group were 3 cases, 36 cases, 21 cases, 3 cases and 61.9%, respectively.There was significant difference between the two groups(χ2=4.589, P=0.032). The improvement rate of life quality of B group(58.7%) was better than A group(33.3%), there was statistically significant difference between the two groups(χ2=9.232, P=0.002). The rates of Ⅲ°﹢Ⅳ°abnormal liver and kidney function, myelosuppression and gastrointestinal tract in A group were 19.0%, 23.8% and 25.4%, those in B group were 15.9%, 20.6% and 30.2%, there were no statistically significant differences between the two groups (P=0.815, P=0.830, P=0.426). Conclusion Hyperthermia combined with chemotherapy is efficient and safe for advanced gastric carcinoma, and it is worthy of furthermore study and observation in clinic. Key words: Hyperthermia, induced; Drug therapy; Stomach neoplasms

Metronomic S-1 dosing and thymidylate synthase silencing have synergistic antitumor efficacy in a colorectal cancer xenograft model

Metronomic chemotherapy is currently considered an emerging therapeutic option in clinical oncology. S-1, an oral formulation of Tegafur (TF), a prodrug of 5-fluorouracil (5-FU), is designed to improve the antitumor activity of 5-FU in tandem with reducing its toxicity. Clinically, metronomic S-1 dosing has been approved for the standard first- and second-line treatment of metastatic or advanced stage of colorectal (CRC). However, expression of intratumor thymidylate synthase (TS), a significant gene in cellular proliferation, is associated with poor outcome to 5-FU-based chemotherapeutic regimens. In this study, therefore, we examined the effect of a combination of TS silencing by an RNA interfering molecule, chemically synthesized short hairpin RNA against TS (shTS), and 5-FU on the growth of human colorectal cancer cell (DLD-1) both in vitro and in vivo. The combined treatment of both shTS with 5-FU substantially inhibited cell proliferation in vitro. For in vivo treatments, the combined treatment of metronomic S-1 dosing with intravenously injected polyethylene glycol (PEG)-coated shTS-lipoplex significantly suppressed tumor growth, compared to a single treatment of either S-1 or PEG-coated shTS-lipoplex. In addition, the combined treatment increased the proportion of apoptotic cells in the DLD-1 tumor tissue. Our results suggest that metronomic S-1 dosing combined with TS silencing might represent an emerging therapeutic strategy for the treatment of patients with advanced CRC.

Cells Cultured on Core-Shell Photonic Crystal Barcodes for Drug Screening.

The development of effective drug screening platforms is an important task for biomedical engineering. Here, a novel methacrylated gelatin (GelMA) hydrogel-encapsulated core-shell photonic crystal (PhC) barcode particle was developed for three-dimensional cell aggregation culture and drug screening. The GelMA shells of the barcode particles enable creation of a three-dimensional extracellular matrix (ECM) microenvironment for cell adhesion and growth, while the PhC cores of the barcode particles provide stable diffraction peaks that can encode different cell spheroids during culture and distinguish their biological response during drug testing. The applicability of this cell spheroids-on-barcodes platform was investigated by testing the cytotoxic effect of tegafur (TF), a prodrug of 5-fluorouracil (5-FU), on barcode particle-loaded liver HepG2 and HCT-116 colonic tumor cell spheroids. The cytotoxicity of TF against the HCT-116 tumor cell spheroids was enhanced in systems using cocultures of HepG2 and NIH-3T3 cells, indicating the effectiveness of this multiple cell spheroids-on-barcodes platform for drug screening.

Clinical effect of oxaliplatin, calcium tolinate and tegafur in the chemotherapy of rectal cancer patients

Objective To observe the effect and toxicity of oxaliplatin combined with calcium folinate and tegafur in the treatment of rectal cancer patients, in order to provide a safe and effective clinical program for rectal cancer treatment. Methods 117 rectal cancer patients conforming to the selection criteria were randomly divided into treatment group 59 cases and control group 58 cases by using random number method, treatment group were received chemotherapy of Oxaliplatin, calcium folinate and tegafur; control group were received FOLFOX4 program. After implementation of two treatment plans, solid tumor curative effect evaluation standard from WHO was referenced to evaluate the curative effect. And toxicity classification was reached according to the WHO cancer drug toxicity assessment standard. Results Total effective rate of treatment group was 27.1%, total effective rate of control group was 29.3%,the comparative difference of two rates was not statistically significant(χ2=0.069,P>0.05). The main symptoms of adverse reactions of two treatment plans were decreased of leukopenia, hemoglobin and thrombocytopenia of the blood system; nausea, vomiting, weak and abnormal liver function of the digestive system;,and limb numbness or pain of the nervous system.Adverse reactions difference in two groups was not significant(χ2=0.106,0.158, 0.000,0.563,0.001,0.284,0.068,0.000,all P>0.05).After treatment,the median surial time was 15.5 months in treatment group and 16.5 months in control group,the difference of the median surial time in two groups was not statistically significant(P=0.781,P>0.05). Conclusion Combination of Oxaliplatin, calcium fluoride and tegafur is another safe and effective plan after the FOLFOX4 program in the treatment of rectal cancer drug application. Key words: Rectal neoplamsms; Oxaliplatin; Tegafur; Calcium Fluoride; FOLFOX4 program

Oxaliplatin combined with tegafur as adjuvant chemotherapy for esophageal squamous cell carcinoma

Objective To investigate the survival benefit of patients with esophageal squamous cell carcinomas who recieved postoperative chemotherapy of tegafur combined with FT-207 radiotherapy. Methods Data from 126 patients with esophageal squamous were analyzed who undergone radical resection from January 2008 to December 2010, consisting of 92 patients underwent surgery alone and 34 patients took oxaliplatin combined with tegafur postoperatively (oxaliplatin 130 g/m2, d1, tegafur 500 mg/m2, d1-5, 21 d for a cycle, every patient received at least two cycles). Results The 1-year survival rate and 3-year survival rate was 93.5 % and 75.0 % in the surgery alone group, was 97.1 % and 76.2 % in the surgery plus postoperative chemotherapy (P=0.590). There was no significant differences in survival in the two groups, even with Cox-regression multivariate analysis and with stratifications of gender, age, tumor location, degree of cell differentiation, invasion depth, lymphatic metastasis and TNM stage. Conclusion Postoperative adjuvant chemotherapy with oxaliplatin combined with tegafur has not significantly improve the survival rate of patients with esophageal squamous cell carcinomas undergoing radical resection. It is still lack of an effective project for postoperative adjuvant chemotherapy for esophageal cancer, and it is necessary for further study. Key words: Esophageal Neoplasms; Adjuvant chemotherapy; Oxaliplatin; Tegafur

Crystal Engineering of Tegafur Cocrystals: Structural Analysis and Physicochemical Properties

Tegafur (TG) is a chemotherapy agent and has been used in the treatment of several common cancerous tumors. Despite wide utility of TG as a main component of the TG-uracil combination drug, TG suff...

Efficacy and Safety of Weekly Liposome-paclitaxel Combined with Tegafur on Metastatic Gastric Cancer

Efficacy and Safety of Weekly Liposome-paclitaxel Combined with Tegafur on Metastatic Gastric Cancer

MgFe2O4@（TF-LDHs）磁性纳米复合体的制备与表征

以镁铁尖晶石(MgFe 2 O 4 )颗粒为磁性基质, 采用共沉淀法制备了替加氟(TF)插层层状双金属氢氧化物(LDHs)包覆MgFe 2 O 4 的核-壳结构磁性纳米复合体[MgFe 2 O 4 @(TF-LDHs)], 并对其化学组成、 晶体结构和磁性等进行了表征, 探讨了TF在LDHs层间的存在状态, 考察了TF的释放行为. 实验结果表明, MgFe 2 O 4 @(TF-LDHs)纳米复合体具有顺磁性, 其比饱和磁化强度随磁性基质含量的增大而增强; TF分子在LDHs层间以长轴略倾斜于LDHs层板的方式呈双层排布; MgFe 2 O 4 @(TF-LDHs)纳米复合体具有明显的药物缓释效果, 其释放动力学过程符合准二级动力学方程, 释放机理为Fick扩散; 增大磁性基质含量或施加外加磁场均可减缓其药物释放过程.

Preliminary Clinical Observation on Irinotecan Combined with Continuous Infusion of Tegafur in Treating Patients with Advanced Colorectal Carcinoma

Objective To observe the availability and the safety of the therapy using Irinotecan combined with continuous infusion of tegafur in advanced colorectal cancer.Method A total of 53 patients were given chemotherapy regimen.That's 150 to 180mg per square meter of Irinotecan parenteral solution,i.v.on day 1 and fuorouracil 200 mg/m2 and Tagafur 2000 mg/m2 civ.48h,on day 1 and day 2.Reiterature per 2 w.To evaluate the near future therapeutic effect according to the RECIST standard and to evaluate the toxic reaction according to the NCI-CTC standard 2w later.Result All patients had total accepted 432 chemotherapy cycles.There 4 to 14 cycles for one patient and the average was 8.2 cycles for one patient.Fifty-one of the patients′ recent therapentic efficacy could be evaluated,and 53 of the patients′ toxic reaction could be evaluated.The overall response rate(RR) was 27.5%,and the disease control rate(DCR) was 66.7%.Three of these gained clinic completed relief,and 11 of these gained partial relief.The TTP was 6.5 m,the common toxic reaction was Leucopenia 43.4%(3.8% in grade Ⅲ) and diarrhea 20.8%.Conclusion The chemotherapy regimen with a combination of Irinotecan and fuorouracil had indeed better therapeutic effect,moreover the toxic reaction was tolerant,reversible and easy to handle,which shows more potential clinic applications.

A Double-modulation Strategy in Cancer Treatment With a Chemotherapeutic Agent and siRNA

5-Fluorouracil (5-FU) is broadly considered the drug of choice for treating human colorectal cancer (CRC). However, 5-FU resistance, mainly caused by the overexpression of antiapoptotic proteins such as Bcl-2, often leads ultimately to treatment failure. We here investigated the effect of Bcl-2 gene silencing, using small interfering RNA (siRNA) (siBcl-2), on the efficacy of 5-FU in CRC. Transfection of siBcl-2 by a Lipofectamine2000/siRNA lipoplex effectively downregulated Bcl-2 expression in the DLD-1 cell line (a CRC), resulting in significant cell growth inhibition in vitro upon treatment with 5-FU. For in vivo treatments, S-1, an oral formulation of Tegafur (TF), a prodrug of 5-FU, was used to mimic 5-FU infusion. The combined treatment of polyethylene glycol (PEG)-coated siBcl-2-lipoplex and S-1 showed superior tumor growth suppression in a DLD-1 xenograft model, compared to each single treatment. Surprisingly, daily S-1 treatment enhanced the accumulation of PEG-coated siBcl-2-lipoplex in tumor tissue. We propose a novel double modulation strategy in cancer treatment, in which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA enhances the chemosensitivity of tumors. Combination of siRNA-containing nanocarriers with chemotherapy may compensate for the limited delivery of siRNA to tumor tissue. In addition, such modulation strategy may be considered a promising therapeutic approach to successfully managing 5-FU-resistant tumors.

Randomized controlled study of oxaliplatin combined with tegafur and calcium folinate in treatment of advanced gastric cancer

Objective To compare the efficacy and safety of oxaliplatin combined with tegafur and calcium folinate with FOLFOX4 regimens on patients with advanced gastric cancer. Methods 120 patients with advanced gastric cancer were randomly divided into two groups. concluding 60 cases in observation group (modified group) treated with oxaliplatin combined with tegafur and leucovorin and 60 cases in control group (FOLFOX4 group) treated with oxaliplatin combined with calcium folinate and fluorouracil. Clinical efficacy was evaluated after 2 (3-6) cycles. Results The clinical efficacy rates of observation group and control group were 63.3 ％ (38/60) and 41.7 ％ (25/60), respectively (x2 =5.647, P =0.028). The median progression-free survival and median overall survival of patients in observation group were 7.7 months and 11.6 months,respectively, and those in control group were 7.3 months and 10.1 months, respectively. The median progression-free survival (P =0.032) and median overall survival (P =0.005) were statistically significant differences. The increased ratio of Karnofsky score of patients in observation group was higher than that in control group (P =0.015). The incidence of myelosuppression in observation group was lower than that in control group (P =0.044). There was no significant difference between the two groups on other adverse reaction rates. Conclusion The efficacy and safety of oxaliplatin plus tegafur and leucovorin in the treatment of advanced gastric cancer is superior to FOLFOX4 regimen, and worthy of clinical application. Key words: Stomach neoplasms; Treatment outcome; Oxaliplatin; Tegafur, Calcium folinate

S-1 in advanced gastric cancer treatment

S-1 is an upgraded product of tegafur and UFT. Compared with 5-FU, it has stronger anticancer activity, and relative rare gastrointestinal adverse reaction. Many clinical studies have demonstrated S-1 has very good efficacy and safety in patients with advanced gastric cancer. The efficacy of single S-1 has been approved better than other available anti-cancer drugs in the treatment of gastric cancer, and similar to combination regimens such as cisplatin plus fluorouracil. Key words: Drug therapy; S-1; Clinical trials

S-1 combined with cisplatin neoadjuvant chemotherapy in gastric carcinoma

S-1 is a kind of fouth-generation oral fluoropyrimidine,including tegafur(FT),5-chloro-2,4-dihydroxypyridine(CDHP),and potassium oxonate(Oxo).S-1 is now used in 80% advanced gastric cancer patients in Japan,it's reported that CR+RR is over 44.6%.Neoadjuvant chemotherapy can reduce tumor loading,degrade the staging,afford operation possibility.S-1 combined with CDDP as a new neoadjuvant chemotherapy,is the most efficient therapy in advanced gastric cancer at present,it's CR can be over 76%. Key words: Chemotherapy,adjuvant; Stomach neoplasms; Cisplatin; S-1

Improved determination of 5‐fluorouracil and its prodrug tegafur in pharmaceuticals by large‐volume sample stacking in CE

On-line determination of the anti-tumor drug 5-fluorouracil (5-FU) and its prodrug, tegafur (TF) was achieved for the first time by capillary electrophoresis with large-volume sample stacking (CE-LVSS). The optimal electrophoretic buffer consisted of 30 mM phosphate buffer at pH 8.0. Without the LVSS procedure, the limits of detection (LOD) were 600.5 ng/mL and 771.4 ng/mL for 5-FU and TF, respectively. With the LVSS procedure, the sensitivity was significantly improved by about two orders of magnitude (the LODs of 5-FU and TF were decreased to 7.9 ng/mL and 6.5 ng/mL, respectively). The %RSD was less than 5%. This method compared favorably with other reported techniques and was applied successfully to the quantitative analysis of anti-tumor drugs in commercial injection preparations. The results show that the method is simple, fast (less than 3 min), highly selective, and sensitive.

Dihydropyrimidine dehydrogenases (DPYD), and cytidine-deaminase (CDA) gene polymorphisms as genomic predictors of clinical outcome in resected gastric cancer patients (GCP) treated with fluoropyrimidine-based adjuvant chemotherapy

4052 Background: Single nucleotide polymorphisms (SNPs) of DPYD gene induces DPD deficiency resulting in decreased activity of 5-fluorouracil derivatives in treatment of colorectal cancer patients (pts). In GCP has not been previously analysed. Methods: We analysed paraffin-embedded biopsies from 50 consecutive resected GCP who received adjuvant chemotherapy with four cycles of Mitomycin C (MMC), 20 mg/m2 iv day 1 plus oral Tegafur (TG), 500 mg/m2 day 1 to day 45 every six weeks, for SNPs of genes DPYD1 (A/G; Ile/Val), DPYD2 (C/T; Arg/Cys) and CDA (A/C; Lys/Gin). The status of alleles (wild type or at least 1 polymorphism) was correlated with outcome, overall survival (OS) and toxicity. Results: The status of SNPs frequencies according to the classification between wild type/non-wild type, were 36/14 in DPYD1; 26/24 in DPYD2; and 17/23 in CDA or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow-up, 18 pts died of tumor relapse, (7 in peritoneum and 11 in distant organs). Difference in survival was observed in DPYD1 pts only, for non wild-type over wild-type (p = 0.0283) and in any of the 3 genes tested heterozygous over homozygous pts (p = 0.0463). In 10 pts (20%) total dose was reduced by toxicity (5 diarrhea, 2 neutropenia, 2 hepatotoxicity, 1 vomiting), only 3 of them were homozygous. Conclusions: SNPs of DPYD1, DPYD2 and CDA predict outcome, survival and toxicity of GCP treated with 5-FU-based adjuvant chemotherapy. No significant financial relationships to disclose.

Thymidylate synthase gene promoter polymorphism in patients with advanced head and neck cancer treated by radio- and 5-fluorouracil chemotherapy

Thymidylate synthase (TS) is a rate-limiting enzyme in the DNA synthetic pathway, and represents a cellular target of antimetabolite drug 5-fluorouracil. It catalyzes the reductive methylation of deoxyuridine-5'-monophosphate to deoxythymidine-5'-monophosphate. Inhibition of TS will result in depletion of both dTMP and, subsequently, dTTP. As a consequence, dUTP is misincorporated into DNA, resulting in DNA breakage and cell death. Developing resistance against 5-fluorouracil (FURA) based drugs might be due to the failure of inhibition of thymidylate synthase enzyme function. In the promoter region of the TS gene there is a tandem repeat sequence (2R or 3R), which was found to be polymorphic and influences the gene expression. Effectiveness and tolerability of Tegafur treatment might be influenced by expression of the TS gene. Our purpose was to determine the effectiveness and tolerability of concomitant radiotherapy and low-dose chemotherapy using Tegafur in respect of promoter polymorphism of thymidilate synthase gene. TS promoter polymorphism (2R/2R, 2R/3R, 3R/3R) was determined by polymerase chain reaction using genomic DNA, in 47 patients with advanced head and neck cancer. Thirty patients out of 47 showed complete response, and genotyping of these patients revealed 2R/2R in 22 (73.3%), 2R/3R in 2 (6.7%) and 3R/3R in 6 (20%). Seventeen out of 47 patients reacted with partial response, and 2R/2R or 2R/3R were revealed in 5 (29.4%) and 3 (17.6%) patients, respectively, and 3R/3R genotype was identified in 9 patients (53%). We did not find any correlation between patient's data and response to therapy, but strong correlation was found between the latter and the patient's genotype. This facts indicate that the analysis of promoter polymorphism of thymidylate synthase gene might be a useful target to examine before FURA-based chemotherapy, and might allow to go into the direction of individualized treatment of head and neck cancer. We suppose that tumor response depends on genomic features of the patients.

Sensitive MS/MS–liquid chromatography assay for simultaneous determination of tegafur, 5-fluorouracil and 5-fluorodihydrouracil in plasma

Ftorafur (FT), an oral prodrug of 5-FU, is part of UFT and S1, two oral prodrugs widely used in digestive tract cancer. We set up a liquid chromatography tandem mass spectrometry (LC/MS-MS) method, chosen for its specificity of detection, for simultaneously measuring in human plasma FT, 5-FU and 5-FUH2. Separation was performed on a Hypercarb column. Linearity, precision and accuracy were validated in the concentration range studied for each compound. This simple and reliable LC/MS-MS method allows specific, sensitive and reproducible quantification of FT, 5-FU and FUH2 in human plasma and can be applied to further pharmacokinetic studies in patients treated with FT-based prodrugs.

Phase II study of weekly irinotecan (CPT-11) associated to protracted oral tegafur (TGF) in previously untreated, advanced colorectal cancer (ACRC)

3725 Background: CPT-11 and 5-fluorouracil (5-FU) are active agents in ACRC. Its combination provides an objective response rate approaching 50%. Oral TGF is a 5-FU prodrug which presents a good sa...