Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response ...Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.展开更多
BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as...BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.展开更多
BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen(TEMCAP)exhibits a certain level of efficacy in treating advanced,welldifferentiated gastroenteropancreatic neuroendocrine tumor...BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen(TEMCAP)exhibits a certain level of efficacy in treating advanced,welldifferentiated gastroenteropancreatic neuroendocrine tumors(GEP-NET).However,published data from Peru are limited.We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population.AIM To evaluate overall survival(OS)in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas(INEN)in Lima-Perú.METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN.A total of thirtyeight patients were included in the final analysis:Thirty-five received TEMCAP as a first-line treatment,and three as a second-line treatment.The primary objective was to evaluate OS.The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression.Survival outcomes were estimated using the Kaplan-Meier method.RESULTS The median age of the patients was 52 years(range 24-77 years),and 53.3%were female.The most common symptoms at diagnosis were abdominal pain in 31 patients(81.6%).Primary tumors included 12 in the rectum(31.6%),11 in the pancreas(28.9%),3 in the ileum(7.9%),2 in the mesentery(5.3%),2 in the small intestine(5.3%),1 in the appendix(2.6%),1 in the stomach(2.6%)and 6 cases of liver metastasis of unknown primary(15.8%).Five were neuroendocrine tumors(NET)G1(13.2%),33 were NET G2(86.8%),five had Ki67<3%(13.2%),and 33 had Ki67 between 3%and 20%(86.8%).TEMCAP was administered to 35(92.1%)patients as first-line treatment.OS at 12,36,and 60 months was estimated in 80%,66%,and 42%,respectively,with a median OS of 49 months.CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible.展开更多
Objective: To examine therapeutic drug monitoring in managing hyperbilirubinemia caused by capecitabine in patients with gastric adenocarcinoma with extensive liver metastases. Results: The initial liver function test...Objective: To examine therapeutic drug monitoring in managing hyperbilirubinemia caused by capecitabine in patients with gastric adenocarcinoma with extensive liver metastases. Results: The initial liver function tests showed an elevation of transaminases (aspartate amino transferase 615 UI/l, alanine aminotransferase 385.9 UI/l), hyperbilirubinemia (total bilirubin at 246.1 μmol/l), and alkaline phosphatase at 694.6 UI/l. We initiated capecitabine based combination chemotherapy, and the clinical pharmacist conducted a full-course medication monitoring of the patient’s treatment including design of individualized dosing regimens and monitoring of bilirubin, infection, cancer pain, parenteral nutrition support and adverse events. After 21 days of supervision by clinical pharmacist and clinicians, the patient’s bilirubin and transaminase decreased progressively, with aspartate aminotransferase, total bilirubin and alkaline phosphatase falling back to 57 UI/l, 69.8 μmol/l, 307.2 UI/l, respectively. The patient’s condition improved significantly at the time of discharge, with the jaundice subsided, and the bloating relieved. Conclusion: Due to adverse reactions, capecitabine requires medication monitoring during use. The relationship between effectiveness and adverse effects is controversial. Adverse reactions should not be the sole criterion for the use of drugs. Clinical pharmacists can improve the safety and effectiveness of patients’ medications and promote rational drug use by monitoring patients, which may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.展开更多
BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the ...BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.展开更多
BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treat...BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.展开更多
Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthrac...Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.展开更多
Aim To measure the penetration of capecitabine from the plasma into tissue and to investigate the pharmacokinetics of its metabolizing into fluorouracil (5-FU) in patients with advanced breast cancer. Methods Twenty...Aim To measure the penetration of capecitabine from the plasma into tissue and to investigate the pharmacokinetics of its metabolizing into fluorouracil (5-FU) in patients with advanced breast cancer. Methods Twenty-seven patients with breast cancer received repeated doses of 1 255 mg·m^-2 of capecitabine twice daily for 7 d. Blood, tumor, and adjacent healthy tissue samples were collected. The concentrations of capecitabine and its metabolite 5-FU were determined by HPLC. The concentration-time profiles of capecitabine and 5-FU were fitted by pharmacokinetic model. The tissue distribution factors for capecitabine and 5-FU, and the AUC ratios of 5-FU to capecitabine in plasma, tumor or adjacent healthy tissue, were calculated with pharmacokinetic parameters, respectively. Results The Ka of capecitabine was 1.17 h^-1 in plasma, 0. 46 h^-1 in tumor tissue, and 0. 61 h^-1 in healthy tissue. The AUCs of capecitabine were 2. 557 1 μg·mL^-1 ·h, 1. 629 2 μg·g^-1·h and 2. 085 0 μg·g^-1· h, and T1/2 was 0. 782 3 h, 1. 528 1 h and 1. 289 6 h in plasma, tumor, and healthy tissue, respectively. The AUCs of 5-FU were 0.418 7 μg·mL^-1 h, 1.671 7 μg·g^-1·h and 1.020 8 μg·g^-1·h; the T1/2 was 0. 631 3 h ,1.204 1 h and 1.031 2 h in plasma, tumor, and healthy tissue, respectively. The tissue distribution factors of capecitabine were 0. 637 1 in tumor (AUCcap-Tumor/AUCcap-plasma) and 0. 851 4 in healthy tissue (AUCcap-HT/AUCcap-plasma . The tissue distribution factors of 5-FU were 3. 992 6 in tumor (AUC5-FU-Tumor/AUC5-FU-plasma) and 2. 438 0 in healthy tissue (AUC5-FU-HT/AUC5-FU-plasma). The AUC ratios of 5-FU to capecitabine were 0. 1637, 1. 0261, and 0. 489 5 in plasma, tumor, and healthy tissue, respectively. Conclusion The simulation curves for the disposition of capecitabine and its metabolite 5-FU in plasma and tissue basically describe the activation process of capecitabine metabolizing to 5-FU and 5-FU elimination. There are similar distributions for capecitabine in plasma, tumor, and healthy tissue. The exposure of 5-FU in tumor was found to be 3. 992 6 times greater than that in plasma and 2. 438 0 times greater than that in healthy tissue. Capecitabine may metabolize preferentially to 5- FU in tumor tissue after oral administration.展开更多
Objective: The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer(MBC...Objective: The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer(MBC).Patients and methods: A total of 98 MBC patients were treated with capecitabine combined with vinorelbine(NX). Results: The median number of treatment was 6 cycles(1-7 cycles). There were two cases of complete remission(CR), 58 partial remission, 27 stable disease(SD), 11 progression disease. The overall response rate(ORR)(CR + PR) was 61.2%. The clinical benefit rate(CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR(CR + PR) was 4%. The CBR was 48%. The median progression-free survival(PFS) was 12 months. In maintenance therapy or not, the median post metastasis survival rate(MSR) was 63 and 28 months, respectively. In the combination therapy group, the major grade 3/4 toxicities included hand-foot syndrome(3.1%), skin pigmentation(2.0%), diarrhoea and abdominal distension(5.1%), stomatitis(1.0%), and leukopenia(20.4%).Conclusions: Capecitabine-based combination therapy and single-agent capecitabine maintenance therapy were well tolerated and effective to MBC.展开更多
Using density functional theory,noncovalent interactions and four mechanisms of covalent functionalization of capecitabine anticancer drug onto γ-Fe2O3 nanoparticles have been investigated.Quantum molecular descripto...Using density functional theory,noncovalent interactions and four mechanisms of covalent functionalization of capecitabine anticancer drug onto γ-Fe2O3 nanoparticles have been investigated.Quantum molecular descriptors of noncovalent configurations were studied.It was specified that binding of capecitabine onto γ-Fe2O3 nanoparticles is thermodynamically suitable.Hardness and the gap of energy between LUMO and HOMO of capecitabine are higher than the noncovalent configurations,showing the reactivity of capecitabine increases in the presence of γ-Fe2O3 nanoparticles.Capecitabine can bond to γ-Fe2O3 nanoparticles through OH(k1 mechanism),NH(k2 mechanism),CO(k3 mechanism) and F(k4 mechanism) groups.The activation energies,activation enthalpies and activation Gibbs free energies of these reactions were calculated.It was specified that the k1 and k2 mechanisms are under thermodynamic control and k3 and k4 under kinetic control.These results could be generalized to other similar drugs.展开更多
Vacuum ultraviolet (VUV) photoionization and dissociative photoionization of capecitabine and its metabolites, 51-deoxy-5-fiuorocytidine (5'-DFCR) and 51-deoxy-5- fiuorouridine (5'- DFUR), were investigated wi...Vacuum ultraviolet (VUV) photoionization and dissociative photoionization of capecitabine and its metabolites, 51-deoxy-5-fiuorocytidine (5'-DFCR) and 51-deoxy-5- fiuorouridine (5'- DFUR), were investigated with infrared laser desorption/tunable synchrotron VUV photoionization mass spectrometry. Molecular ions (M+) with small amounts of fragments can be found for these compounds at relatively low photon energies, while more fragment ions would be produced by increasing the photon energies. (M-H2O)+, (base+H)+, (base+2H)+, (base+30)+, (base+60)+, and sugar moiety were proposed for these nucleoside drugs with similar backbones. Decomposition channels for the major fragments were discussed in detail. Moreover, ab initio calculations were introduced to study the dehydration pathways of three fluoro-nucleosides. Corresponding appearance energies for the (M-H2O)+ ions were computed.展开更多
AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database wer...AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients.Statistical analysis was performed by metaanalysis.Four randomized controlled trials met the inclusion criteria.RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80(95%CI: 0.52-1.21, P = 0.29).The overall response rate of S-1 vs capecitabine was 0.94(95%CI: 0.59-1.51, P = 0.93).Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia( O R = 0.9 9, 9 5 % C I : 0.6 5- 1.4 9, P = 0.9 4) a n d thrombocytopenia(OR = 0.72, 95%CI: 0.31-1.67, P = 0.44).The most frequent non-hematologic toxicities included nausea(OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome(OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001).CONCLUSION: The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.展开更多
Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric...Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.展开更多
AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic ...AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.展开更多
AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a ...AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage Ⅳ gastric cancer. In particular, 30 or 40 mg/m^2 of docetaxel on day 1, 60 mg/m^2 of cisplatin on day 1, and 2000 mg/m^2 of capecitabine for 2 wk were administered every three weeks.RESULTS Three patients were treated with modified DCX(m DCX) with 30 mg/m^2 docetaxel, and five patients were treated with this regimen with 40 mg/m^2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes.CONCLUSION m DCX was well tolerated by Japanese patients with stage Ⅳ gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.展开更多
Fluoropyrimidines play a central role in the first-line treatment of metastatic colorectal cancer. Our aim was to review whether capecitabine was a safer, non-inferior, economically superior and more convenient altern...Fluoropyrimidines play a central role in the first-line treatment of metastatic colorectal cancer. Our aim was to review whether capecitabine was a safer, non-inferior, economically superior and more convenient alternative to 5-fluorouracil. Capecitabine has previously been compared to 5-fluorouracil-either as a monotherapy or in combination with oxaliplatin, irinotecan, or biological drugs-and has been found to have comparable efficacy and safety profiles. Furthermore, pharmacoeconomic data and patients’ preferences for oral chemotherapy further favor capecitabine. Therefore, capecitabine appears to be an effective and safe alternative to fluorouracil in the first-line treatment of metastatic colorectal cancer.展开更多
AIM: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of capecitabine combined with postoperative radiotherapy for gastric cancer.
AIM:To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer(ESCC) and the survival of the patients.METHODS:Sixty...AIM:To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer(ESCC) and the survival of the patients.METHODS:Sixty-four patients(median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy.Each patient received at least two cycles of treatment.The efficacy,side effects and patient survival were evaluated.RESULTS:The partial response(PR) rate was 43.8%(28/64).Stable disease(SD) rate was 47.9%(26/64),and disease progression rate was 15.6%(10/64).The clinical benefit rate(PR + SD) was 84.4%.The main toxicities were leukopenia(50.0%),nausea and vomiting(51.6%),diarrhea(50.0%),stomatitis(39.1%),polyneuropathy(37.5%) and hand-foot syndrome(37.5%).No grade 4 event in the entire cohort was found.The median progression-free survival was 4 mo,median overall survival was 10 mo(95% CI:8.3-11.7 mo),and the 1-and 2-year survival rates were 38.1% and 8.2%,respectively.High Karnofsky index,single metastatic lesion and response to the regimen indicated respectively good prognosis.CONCLUSION:Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients.The regimen has improved the survival moderately and merits further studies.展开更多
AIM To investigate the feasibility of preoperative docetaxel,cisplatin and capecitabine(DCC) in patients with resectable gastric cancer.METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria...AIM To investigate the feasibility of preoperative docetaxel,cisplatin and capecitabine(DCC) in patients with resectable gastric cancer.METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria,were treated with 4 cycles of docetaxel(60 mg/m2),cisplatin(60 mg/m2) and capecitabine(1.875 mg/m2 orally on day 1-14,two daily doses) repeated every three weeks,followed by surgery.Primary end point was the feasibility and toxicity/safety profile of DCC,secondary endpoints were pathological complete resection rate and pathological complete response(p CR) rate.RESULTS All of the patients(51) were assessable for the feasibility and safety of the regimen.The entire preoperative regimen was completed by 68.6% of the patients.Grade Ⅲ/Ⅳ febrile neutropenia occurred in 10% of all courses.Three patients died due to treatment related toxicity(5.9%),one of them(also) because of refusing further treatment for toxicity.Of the 45 patients who were evaluable for secondary endpoints,four developed metastatic disease and 76.5% received a curative resection.In 3 patients a p CR was seen(5.9%),two patients underwent a R1 resection(3.9%).CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding.The high occurrence of febrile neutropenia is of concern.To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colonystimulating factor(G-CSF) should be explored.A curative resection rate of 76.5% is acceptable.The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.展开更多
Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the e...Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC.The primary endpoint was clinical benefit rate(CBR).Secondary endpoints included progression-free survival(PFS),time to response(TTR),duration of response(DoR),central nervous system(CNS) as first site of relapse,and safety.The results showed that there were 23 patients with partial responses and 7 patients with stable disease,resulting in a CBR of 57.7%.The median PFS was 6.34 months(95% confidence interval,4.93-9.82 months).The median TTR and DoR were 4.07 months(range,0.03-14.78 months) and 6.93 months(range,1.45-9.72 months),respectively.Thirteen(25.0%) patients had new lesions as disease progression.Among them,2(3.8%) patients had CNS disease reported as the first relapse.The most common toxicities were palmar-plantar erythrodysesthesia(59.6%),diarrhea(48.1%),rash(48.1%),hyperbilirubinemia(34.6%),and fatigue(30.8%).Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample,baseline PIK3CA mutation status was not associated with CBR(P = 0.639) or PFS(P = 0.989).These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC,irrespective of PIK3CA status.展开更多
基金supported by grants from Sanming Project of Medicine in Shenzhen(No.SZSM202211030)the Science and Technology Department Basic Research Project of Shanxi(No.202203021221284)。
文摘Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.
文摘BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.
文摘BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen(TEMCAP)exhibits a certain level of efficacy in treating advanced,welldifferentiated gastroenteropancreatic neuroendocrine tumors(GEP-NET).However,published data from Peru are limited.We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population.AIM To evaluate overall survival(OS)in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas(INEN)in Lima-Perú.METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN.A total of thirtyeight patients were included in the final analysis:Thirty-five received TEMCAP as a first-line treatment,and three as a second-line treatment.The primary objective was to evaluate OS.The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression.Survival outcomes were estimated using the Kaplan-Meier method.RESULTS The median age of the patients was 52 years(range 24-77 years),and 53.3%were female.The most common symptoms at diagnosis were abdominal pain in 31 patients(81.6%).Primary tumors included 12 in the rectum(31.6%),11 in the pancreas(28.9%),3 in the ileum(7.9%),2 in the mesentery(5.3%),2 in the small intestine(5.3%),1 in the appendix(2.6%),1 in the stomach(2.6%)and 6 cases of liver metastasis of unknown primary(15.8%).Five were neuroendocrine tumors(NET)G1(13.2%),33 were NET G2(86.8%),five had Ki67<3%(13.2%),and 33 had Ki67 between 3%and 20%(86.8%).TEMCAP was administered to 35(92.1%)patients as first-line treatment.OS at 12,36,and 60 months was estimated in 80%,66%,and 42%,respectively,with a median OS of 49 months.CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible.
文摘Objective: To examine therapeutic drug monitoring in managing hyperbilirubinemia caused by capecitabine in patients with gastric adenocarcinoma with extensive liver metastases. Results: The initial liver function tests showed an elevation of transaminases (aspartate amino transferase 615 UI/l, alanine aminotransferase 385.9 UI/l), hyperbilirubinemia (total bilirubin at 246.1 μmol/l), and alkaline phosphatase at 694.6 UI/l. We initiated capecitabine based combination chemotherapy, and the clinical pharmacist conducted a full-course medication monitoring of the patient’s treatment including design of individualized dosing regimens and monitoring of bilirubin, infection, cancer pain, parenteral nutrition support and adverse events. After 21 days of supervision by clinical pharmacist and clinicians, the patient’s bilirubin and transaminase decreased progressively, with aspartate aminotransferase, total bilirubin and alkaline phosphatase falling back to 57 UI/l, 69.8 μmol/l, 307.2 UI/l, respectively. The patient’s condition improved significantly at the time of discharge, with the jaundice subsided, and the bloating relieved. Conclusion: Due to adverse reactions, capecitabine requires medication monitoring during use. The relationship between effectiveness and adverse effects is controversial. Adverse reactions should not be the sole criterion for the use of drugs. Clinical pharmacists can improve the safety and effectiveness of patients’ medications and promote rational drug use by monitoring patients, which may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.
基金Supported by National Key Research and Development Program of China,No.2020YFA0710802The Youth Science Fund of the Nature Science Foundation of Tianjin,No.20JCQNJC01370+1 种基金The Key Projects of Tianjin Science and Technology Project,No.21JCZDJC00160The Science Foundation of Tianjin Health Commission,No.ZC20065 and No.ZC20089.
文摘BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.
基金The study was reviewed and approved by the Rabin Medical Center Institutional Review Board(Approval No.0639-19-RMC).
文摘BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.
基金This work was sup-ported by National Natural Sclence Foundatlon of China(no.81202108)
文摘Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.
文摘Aim To measure the penetration of capecitabine from the plasma into tissue and to investigate the pharmacokinetics of its metabolizing into fluorouracil (5-FU) in patients with advanced breast cancer. Methods Twenty-seven patients with breast cancer received repeated doses of 1 255 mg·m^-2 of capecitabine twice daily for 7 d. Blood, tumor, and adjacent healthy tissue samples were collected. The concentrations of capecitabine and its metabolite 5-FU were determined by HPLC. The concentration-time profiles of capecitabine and 5-FU were fitted by pharmacokinetic model. The tissue distribution factors for capecitabine and 5-FU, and the AUC ratios of 5-FU to capecitabine in plasma, tumor or adjacent healthy tissue, were calculated with pharmacokinetic parameters, respectively. Results The Ka of capecitabine was 1.17 h^-1 in plasma, 0. 46 h^-1 in tumor tissue, and 0. 61 h^-1 in healthy tissue. The AUCs of capecitabine were 2. 557 1 μg·mL^-1 ·h, 1. 629 2 μg·g^-1·h and 2. 085 0 μg·g^-1· h, and T1/2 was 0. 782 3 h, 1. 528 1 h and 1. 289 6 h in plasma, tumor, and healthy tissue, respectively. The AUCs of 5-FU were 0.418 7 μg·mL^-1 h, 1.671 7 μg·g^-1·h and 1.020 8 μg·g^-1·h; the T1/2 was 0. 631 3 h ,1.204 1 h and 1.031 2 h in plasma, tumor, and healthy tissue, respectively. The tissue distribution factors of capecitabine were 0. 637 1 in tumor (AUCcap-Tumor/AUCcap-plasma) and 0. 851 4 in healthy tissue (AUCcap-HT/AUCcap-plasma . The tissue distribution factors of 5-FU were 3. 992 6 in tumor (AUC5-FU-Tumor/AUC5-FU-plasma) and 2. 438 0 in healthy tissue (AUC5-FU-HT/AUC5-FU-plasma). The AUC ratios of 5-FU to capecitabine were 0. 1637, 1. 0261, and 0. 489 5 in plasma, tumor, and healthy tissue, respectively. Conclusion The simulation curves for the disposition of capecitabine and its metabolite 5-FU in plasma and tissue basically describe the activation process of capecitabine metabolizing to 5-FU and 5-FU elimination. There are similar distributions for capecitabine in plasma, tumor, and healthy tissue. The exposure of 5-FU in tumor was found to be 3. 992 6 times greater than that in plasma and 2. 438 0 times greater than that in healthy tissue. Capecitabine may metabolize preferentially to 5- FU in tumor tissue after oral administration.
文摘Objective: The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer(MBC).Patients and methods: A total of 98 MBC patients were treated with capecitabine combined with vinorelbine(NX). Results: The median number of treatment was 6 cycles(1-7 cycles). There were two cases of complete remission(CR), 58 partial remission, 27 stable disease(SD), 11 progression disease. The overall response rate(ORR)(CR + PR) was 61.2%. The clinical benefit rate(CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR(CR + PR) was 4%. The CBR was 48%. The median progression-free survival(PFS) was 12 months. In maintenance therapy or not, the median post metastasis survival rate(MSR) was 63 and 28 months, respectively. In the combination therapy group, the major grade 3/4 toxicities included hand-foot syndrome(3.1%), skin pigmentation(2.0%), diarrhoea and abdominal distension(5.1%), stomatitis(1.0%), and leukopenia(20.4%).Conclusions: Capecitabine-based combination therapy and single-agent capecitabine maintenance therapy were well tolerated and effective to MBC.
文摘Using density functional theory,noncovalent interactions and four mechanisms of covalent functionalization of capecitabine anticancer drug onto γ-Fe2O3 nanoparticles have been investigated.Quantum molecular descriptors of noncovalent configurations were studied.It was specified that binding of capecitabine onto γ-Fe2O3 nanoparticles is thermodynamically suitable.Hardness and the gap of energy between LUMO and HOMO of capecitabine are higher than the noncovalent configurations,showing the reactivity of capecitabine increases in the presence of γ-Fe2O3 nanoparticles.Capecitabine can bond to γ-Fe2O3 nanoparticles through OH(k1 mechanism),NH(k2 mechanism),CO(k3 mechanism) and F(k4 mechanism) groups.The activation energies,activation enthalpies and activation Gibbs free energies of these reactions were calculated.It was specified that the k1 and k2 mechanisms are under thermodynamic control and k3 and k4 under kinetic control.These results could be generalized to other similar drugs.
文摘Vacuum ultraviolet (VUV) photoionization and dissociative photoionization of capecitabine and its metabolites, 51-deoxy-5-fiuorocytidine (5'-DFCR) and 51-deoxy-5- fiuorouridine (5'- DFUR), were investigated with infrared laser desorption/tunable synchrotron VUV photoionization mass spectrometry. Molecular ions (M+) with small amounts of fragments can be found for these compounds at relatively low photon energies, while more fragment ions would be produced by increasing the photon energies. (M-H2O)+, (base+H)+, (base+2H)+, (base+30)+, (base+60)+, and sugar moiety were proposed for these nucleoside drugs with similar backbones. Decomposition channels for the major fragments were discussed in detail. Moreover, ab initio calculations were introduced to study the dehydration pathways of three fluoro-nucleosides. Corresponding appearance energies for the (M-H2O)+ ions were computed.
文摘AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients.Statistical analysis was performed by metaanalysis.Four randomized controlled trials met the inclusion criteria.RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80(95%CI: 0.52-1.21, P = 0.29).The overall response rate of S-1 vs capecitabine was 0.94(95%CI: 0.59-1.51, P = 0.93).Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia( O R = 0.9 9, 9 5 % C I : 0.6 5- 1.4 9, P = 0.9 4) a n d thrombocytopenia(OR = 0.72, 95%CI: 0.31-1.67, P = 0.44).The most frequent non-hematologic toxicities included nausea(OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome(OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001).CONCLUSION: The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.
基金supported by the National "863" High‐Tech Res & Dev Program of China (No. 2006AA02A402)Beijing Municipal Science & Technology Commission Program "Optimization of pharmacotherapy and individual selection in gastric cancer" (No D101100050010023)
文摘Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.
基金Supported by Shanghai Municipal Health Bureau Outstanding Young Clinical Personal Training Project, No. ZYSNXD-YLYSZK025
文摘AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.
文摘AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage Ⅳ gastric cancer. In particular, 30 or 40 mg/m^2 of docetaxel on day 1, 60 mg/m^2 of cisplatin on day 1, and 2000 mg/m^2 of capecitabine for 2 wk were administered every three weeks.RESULTS Three patients were treated with modified DCX(m DCX) with 30 mg/m^2 docetaxel, and five patients were treated with this regimen with 40 mg/m^2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes.CONCLUSION m DCX was well tolerated by Japanese patients with stage Ⅳ gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.
文摘Fluoropyrimidines play a central role in the first-line treatment of metastatic colorectal cancer. Our aim was to review whether capecitabine was a safer, non-inferior, economically superior and more convenient alternative to 5-fluorouracil. Capecitabine has previously been compared to 5-fluorouracil-either as a monotherapy or in combination with oxaliplatin, irinotecan, or biological drugs-and has been found to have comparable efficacy and safety profiles. Furthermore, pharmacoeconomic data and patients’ preferences for oral chemotherapy further favor capecitabine. Therefore, capecitabine appears to be an effective and safe alternative to fluorouracil in the first-line treatment of metastatic colorectal cancer.
基金Supported by Beijing Hope Run Special Fund,No.LC2007A03
文摘AIM: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of capecitabine combined with postoperative radiotherapy for gastric cancer.
文摘AIM:To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer(ESCC) and the survival of the patients.METHODS:Sixty-four patients(median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy.Each patient received at least two cycles of treatment.The efficacy,side effects and patient survival were evaluated.RESULTS:The partial response(PR) rate was 43.8%(28/64).Stable disease(SD) rate was 47.9%(26/64),and disease progression rate was 15.6%(10/64).The clinical benefit rate(PR + SD) was 84.4%.The main toxicities were leukopenia(50.0%),nausea and vomiting(51.6%),diarrhea(50.0%),stomatitis(39.1%),polyneuropathy(37.5%) and hand-foot syndrome(37.5%).No grade 4 event in the entire cohort was found.The median progression-free survival was 4 mo,median overall survival was 10 mo(95% CI:8.3-11.7 mo),and the 1-and 2-year survival rates were 38.1% and 8.2%,respectively.High Karnofsky index,single metastatic lesion and response to the regimen indicated respectively good prognosis.CONCLUSION:Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients.The regimen has improved the survival moderately and merits further studies.
文摘AIM To investigate the feasibility of preoperative docetaxel,cisplatin and capecitabine(DCC) in patients with resectable gastric cancer.METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria,were treated with 4 cycles of docetaxel(60 mg/m2),cisplatin(60 mg/m2) and capecitabine(1.875 mg/m2 orally on day 1-14,two daily doses) repeated every three weeks,followed by surgery.Primary end point was the feasibility and toxicity/safety profile of DCC,secondary endpoints were pathological complete resection rate and pathological complete response(p CR) rate.RESULTS All of the patients(51) were assessable for the feasibility and safety of the regimen.The entire preoperative regimen was completed by 68.6% of the patients.Grade Ⅲ/Ⅳ febrile neutropenia occurred in 10% of all courses.Three patients died due to treatment related toxicity(5.9%),one of them(also) because of refusing further treatment for toxicity.Of the 45 patients who were evaluable for secondary endpoints,four developed metastatic disease and 76.5% received a curative resection.In 3 patients a p CR was seen(5.9%),two patients underwent a R1 resection(3.9%).CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding.The high occurrence of febrile neutropenia is of concern.To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colonystimulating factor(G-CSF) should be explored.A curative resection rate of 76.5% is acceptable.The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.
文摘Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC.The primary endpoint was clinical benefit rate(CBR).Secondary endpoints included progression-free survival(PFS),time to response(TTR),duration of response(DoR),central nervous system(CNS) as first site of relapse,and safety.The results showed that there were 23 patients with partial responses and 7 patients with stable disease,resulting in a CBR of 57.7%.The median PFS was 6.34 months(95% confidence interval,4.93-9.82 months).The median TTR and DoR were 4.07 months(range,0.03-14.78 months) and 6.93 months(range,1.45-9.72 months),respectively.Thirteen(25.0%) patients had new lesions as disease progression.Among them,2(3.8%) patients had CNS disease reported as the first relapse.The most common toxicities were palmar-plantar erythrodysesthesia(59.6%),diarrhea(48.1%),rash(48.1%),hyperbilirubinemia(34.6%),and fatigue(30.8%).Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample,baseline PIK3CA mutation status was not associated with CBR(P = 0.639) or PFS(P = 0.989).These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC,irrespective of PIK3CA status.