Preventing the recurrence of lung oligometastases after local therapy in patients with colorectal cancer is an area requiring investigation.A recent article demonstrated that adding capecitabine maintenance therapy af...Preventing the recurrence of lung oligometastases after local therapy in patients with colorectal cancer is an area requiring investigation.A recent article demonstrated that adding capecitabine maintenance therapy after radiofrequency ablation improved the 5-year overall survival(88.7%vs 69.1%)and reduced local tumor progression(22.7%vs 49.0%)compared with radiofrequency ablation alone.Although progression-free survival did not differ significantly between the two treatments,multivariate analysis confirmed a robust survival benefit.These findings support the use of systemic maintenance to eradicate micrometastases after locoregional control and warrant validation in prospective randomized trials.展开更多
A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive...A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.展开更多
BACKGROUND No clear guidelines for long-term postoperative maintenance therapy have been established for patients with lung oligometastases from colorectal cancer(CRC)who achieve radiological no evidence of disease af...BACKGROUND No clear guidelines for long-term postoperative maintenance therapy have been established for patients with lung oligometastases from colorectal cancer(CRC)who achieve radiological no evidence of disease after radiofrequency ablation(RFA)treatment.We compared the outcomes of patients with lung oligometa-stases from CRC after RFA plus maintenance capecitabine with RFA alone.AIM To determine whether adding capecitabine to RFA improves prognosis compared with RFA alone.METHODS This multicenter retrospective study included consecutive patients from two tertiary cancer centers treated for pulmonary oligometastases from CRC between 2016 and 2023.Subjects were assigned to RFA plus capecitabine(combined)or RFA alone(only RFA)groups.Primary outcomes included overall survival(OS)and progression-free survival(PFS)survival and the secondary outcome was local tumor progression(LTP).The OS,PFS,and LTP rates were compared between the two groups.In addition,prognostic factors were identified using univariate and multivariate analyses.RESULTS Combination therapy(RFA+capecitabine,n=148)and RFA monotherapy(n=99)were compared in patients with CRC and lung metastases.The median OS was 37.8 months(22.4,50.3),the PFS was 18.7 months(13.0,36.5),and the LTP was 31.5 months(20.0,52.4)in the Only RFA group.The OS increased significantly(P=0.011)and the LTP decreased at all time points(P<0.001)in the combined group.The multivariate cox analysis revealed that combined chemotherapy significantly improved OS,with hazard ratios ranging from 0.29 to 0.35(all P<0.015)after adjusting for demographic,tumor,and treatment-related factors.The risk of death was consistently lower in the combination therapy group compared to RFA monotherapy.CONCLUSION RFA prolongs survival and local control in patients with CRC pulmonary oligometastases.Adjuvant capecitabine increases OS and reduces LTP compared to RFA alone,but PFS did not significantly change.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
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
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
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 plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced o...AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient clinics.Patients received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 toxicity.The treatment choice of bevacizumab was at the discretion of the physician.Theprimary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,respectively.No complete responses were observed.The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,respectively.The median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically different.In the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting.Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.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
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
Objective： To investigate the efficacy and safety of capecitabine maintenance therapy（MT） after initial capecitabine plus docetaxel（XT） chemotherapy in patients with metastatic triple-negative breast cancer（m T...Objective： To investigate the efficacy and safety of capecitabine maintenance therapy（MT） after initial capecitabine plus docetaxel（XT） chemotherapy in patients with metastatic triple-negative breast cancer（m TNBC）.Methods： Fifty-five m TNBC patients treated with XT chemotherapy between May 2007 and June 2013 were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, capecitabine was continued for 32 patients（MT）, while 23 patients remained without any treatment（nonMT）. We compared progression-free survival（PFS） and safety of both groups.Results： The median PFS of 55 patients was 8.1 months, overall median PFS time of 32 patients in the capecitabine MT group and 23 in the non-MT group was 10.1 vs. 6.7 months（P=0.032）, respectively. When compared PFS time of maintenance treatment, single-agent capecitabine prolonged PFS by 7.1 months, for non-MT patients, the PFS without any treatment was 3.1 months, and this between-group difference was statistically significant（P=0.003）. Adverse events, including of hematologic toxicity, gastrointestinal toxicities, hand-foot syndrome and abnormal liver function were not significantly different between two groups.Conclusions： After initial disease control was achieved with the XT combination chemotherapy, capecitabine MT can significantly prolong PFS time with a favorable safety profile in m TNBC patients.展开更多
AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chem...AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers.RESULTS:A total of 108 patients were reviewed.Median age at diagnosis was 60.The majority of the patients(64.8%) had advanced stage Ⅲ and Ⅳ disease(with no distant metastasis).All except 4 patients had D2 gastrectomy.Twenty one patients(19.4%) had positive surgical resection margins.Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone.For the patients in the chemotherapy-only group,all had fluoropyrimidine-based therapy,with added cisplatin in 7 patients and epirubicin in 2 patients.Median recurrence-free survival was longer for the XRT group(52 mo) compared to the 5FU-RT(35 mo) and chemotherapy-only groups(25 mo)(P=0.48).The patients in the XRT group achieved similar median overall survival(53 mo) as the 5FU-RT(54 mo) and the chemotherapy-only groups(44 mo)(P=0.5).CONCLUSION:Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.展开更多
Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates. To improve long-term outcomes, perioperative chemotherapies are combined with surgery. Human epidermal growth factor r...Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates. To improve long-term outcomes, perioperative chemotherapies are combined with surgery. Human epidermal growth factor receptor 2 (HER2) overexpression had been noted in gastric cancer; therefore, trastuzumab has been used occasionally in this setting. A 63-year-old male Chinese patient, who was diagnosed with adenocarcinoma in the gastric antrum, as well as lymph node metastases along the left gastric and hepatic artery, and left adrenal area, was admitted to our hospital. HER2 expression was positive, and cluster amplification was detected in a fluorescence in situ hybridization assay. The patient received three cycles of a neoadjuvant trastuzumab/oxaliplatin /capecitabine regimen. He subsequently underwent distal gastrectomy, D2+ lymphadenectomy, left adrenalectomy, cholecystectomy and Billroth II anastomosis. Treatment was continued with another five postoperative cycles of the same medication and trastuzumab application for 1 year. No recurrence has been observed 18 mo after the operation. Trastuzumab as perioperative and adjuvant medication, in combination with oxaliplatin and capecitabine for a HER2-overexpressing advanced gastric adenocarcinoma, led to recurrence-free survival of at least 18 mo after surgery.展开更多
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
Capecitabine (Xeloda) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specif ic conversion to the a...Capecitabine (Xeloda) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specif ic conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capecitabine with standard folinic acid (leucovorin, LV)-modulated intravenous 5-fluorouracil (5-FU) bolus regimens in patients with metastatic colorectal cancer. Moreover the efficacy of Capecitabine on metastatic colorectal cancer, either alone or in various combinations with other active drugs such as Irinotecan and Oxaliplatin was also assessed. Finally, neoadjuvant therapy con- sisting of Capecitabine plus radiation therapy, for locally advanced rectal cancer was analysed. This combination of chemotherapy and radiotherapy has a special role in tumor down staging and in sphincter preservation for lower rectal tumors. Comparative trials have shown that Capecitabine is at least equivalent to the standard LV-5-FU combination in relation to progression-free and overall survival whilst showing a better tolerability prof ile with a much lower incidence of stomatitis. It is now known that Capecitabine can be combined with other active drugs such as Irinotecan and Oxaliplatin. The combination of Oxaliplatin with Capecitabine represents a new standard of care for metastatic colorectal cancer. Combinating the Capecitabine-Oxaliplatin regimen with promising new biological drugs such as Bevacizumab seems to give a realistic prospect of further improvement in time to progression of metastatic disease. Moreover, preoperative chemo-radiation using oral capecitabine is better tolerated than bolus 5-FU and is more effective in the promotion of both down-staging and sphincter preservation in patients with locally advanced rectal cancer. Finally, the outcomes of recently published trials suggest that capecitabine seems to be more cost effective than other standard treatments for the management of patients with colorectal cancer.展开更多
Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC) patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from...Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC) patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from first-line chemotherapy,patients with mCRC in our hospital received two different treatment strategies.Thirty-three patients in maintenance group were treated with capecitabine 1000 mg/m2 po bid d1-14,q21d.Fifty-two patients in non-maintenance group did not receive any further chemotherapy.Results:Patients in maintenance group and non-maintenance group both received FOLFOX,FOLFIRI and XELOX as first-line therapy.The median chemotherapy cycles the two groups received were the same(6 vs 6).The response rates of first-line chemotherapy were 33.3% in maintenance group and 32.7% in non-maintenance group.Patients in maintenance group received 3-9 cycles of capecitabine therapy(median cycle 4).29/33(87.9%) patients in maintenance group and 47/52(90.4%) in non-maintenance group received following second-line chemotherapy,and no patients underwent targeted therapy.The median survival time and TTP were 40.4 months(95%CI:24.2-56.6) and 9.0 months(95%CI:6.7-11.3) in maintenance group,as compared with 21.5 months(95%CI:14.9-28.0,P=0.015) and 6.5 months(95%CI:4.4-8.5,P=0.007) in non-maintenance group.No severe adverse event was observed in the capecitabine maintenance group.Conclusion:mCRC patients could benefit from capecitabine maintenance therapy by prolonging survival time and TTP.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
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 Capecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer.The most frequently reported adverse events attribut...BACKGROUND Capecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer.The most frequently reported adverse events attributed to capecitabine include diarrhea,hyperbilirubinemia,and hand-foot syndrome(HFS).A number of cutaneous adverse events have been attributed to capecitabine,including Stevens-Johnson syndrome(SJS)as a rare and potentially life-threatening mucocutaneous condition.We report the first case involving concurrent SJS and HFS after capecitabine and lapatinib treatment.CASE SUMMARY A 70-year-old woman with a history of breast cancer treatment visited our hospital for evaluation of painful skin lesions.Six weeks earlier,she had been prescribed capecitabine plus lapatinib as treatment for metastatic breast cancer.She subsequently developed worsening erythema and bullae on her palms and soles,as well as reddish macules on her back and chest wall.Histopathological evaluation of the chest wall lesions revealed extensive eosinophilic epidermal necrosis and separation of the epidermis from the dermis.The capecitabine plus lapatinib treatment was discontinued immediately and treatment was started using systemic steroids.This treatment resolved most lesions,although the lesions on her palms and soles required Vaseline gauze dressings,which resulted in reepithelialization.Therefore,we determined that the patient had concurrent SJS and HFS.Although the dermatological problems resolved,the patient ultimately died because of multiple organ failure.CONCLUSION Oral capecitabine treatment carries a risk of both HFS and also life-threatening adverse cutaneous drug reactions,such as SJS.展开更多
文摘Preventing the recurrence of lung oligometastases after local therapy in patients with colorectal cancer is an area requiring investigation.A recent article demonstrated that adding capecitabine maintenance therapy after radiofrequency ablation improved the 5-year overall survival(88.7%vs 69.1%)and reduced local tumor progression(22.7%vs 49.0%)compared with radiofrequency ablation alone.Although progression-free survival did not differ significantly between the two treatments,multivariate analysis confirmed a robust survival benefit.These findings support the use of systemic maintenance to eradicate micrometastases after locoregional control and warrant validation in prospective randomized trials.
文摘A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.
基金Supported by the National Natural Science Foundation of China,No.82072034。
文摘BACKGROUND No clear guidelines for long-term postoperative maintenance therapy have been established for patients with lung oligometastases from colorectal cancer(CRC)who achieve radiological no evidence of disease after radiofrequency ablation(RFA)treatment.We compared the outcomes of patients with lung oligometa-stases from CRC after RFA plus maintenance capecitabine with RFA alone.AIM To determine whether adding capecitabine to RFA improves prognosis compared with RFA alone.METHODS This multicenter retrospective study included consecutive patients from two tertiary cancer centers treated for pulmonary oligometastases from CRC between 2016 and 2023.Subjects were assigned to RFA plus capecitabine(combined)or RFA alone(only RFA)groups.Primary outcomes included overall survival(OS)and progression-free survival(PFS)survival and the secondary outcome was local tumor progression(LTP).The OS,PFS,and LTP rates were compared between the two groups.In addition,prognostic factors were identified using univariate and multivariate analyses.RESULTS Combination therapy(RFA+capecitabine,n=148)and RFA monotherapy(n=99)were compared in patients with CRC and lung metastases.The median OS was 37.8 months(22.4,50.3),the PFS was 18.7 months(13.0,36.5),and the LTP was 31.5 months(20.0,52.4)in the Only RFA group.The OS increased significantly(P=0.011)and the LTP decreased at all time points(P<0.001)in the combined group.The multivariate cox analysis revealed that combined chemotherapy significantly improved OS,with hazard ratios ranging from 0.29 to 0.35(all P<0.015)after adjusting for demographic,tumor,and treatment-related factors.The risk of death was consistently lower in the combination therapy group compared to RFA monotherapy.CONCLUSION RFA prolongs survival and local control in patients with CRC pulmonary oligometastases.Adjuvant capecitabine increases OS and reduces LTP compared to RFA alone,but PFS did not significantly change.
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.
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.
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 The companies Pfizer and Roche provided partial support for the study and data monitoring
文摘AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient clinics.Patients received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 toxicity.The treatment choice of bevacizumab was at the discretion of the physician.Theprimary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,respectively.No complete responses were observed.The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,respectively.The median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically different.In the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting.Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.
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 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Objective： To investigate the efficacy and safety of capecitabine maintenance therapy（MT） after initial capecitabine plus docetaxel（XT） chemotherapy in patients with metastatic triple-negative breast cancer（m TNBC）.Methods： Fifty-five m TNBC patients treated with XT chemotherapy between May 2007 and June 2013 were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, capecitabine was continued for 32 patients（MT）, while 23 patients remained without any treatment（nonMT）. We compared progression-free survival（PFS） and safety of both groups.Results： The median PFS of 55 patients was 8.1 months, overall median PFS time of 32 patients in the capecitabine MT group and 23 in the non-MT group was 10.1 vs. 6.7 months（P=0.032）, respectively. When compared PFS time of maintenance treatment, single-agent capecitabine prolonged PFS by 7.1 months, for non-MT patients, the PFS without any treatment was 3.1 months, and this between-group difference was statistically significant（P=0.003）. Adverse events, including of hematologic toxicity, gastrointestinal toxicities, hand-foot syndrome and abnormal liver function were not significantly different between two groups.Conclusions： After initial disease control was achieved with the XT combination chemotherapy, capecitabine MT can significantly prolong PFS time with a favorable safety profile in m TNBC patients.
文摘AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers.RESULTS:A total of 108 patients were reviewed.Median age at diagnosis was 60.The majority of the patients(64.8%) had advanced stage Ⅲ and Ⅳ disease(with no distant metastasis).All except 4 patients had D2 gastrectomy.Twenty one patients(19.4%) had positive surgical resection margins.Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone.For the patients in the chemotherapy-only group,all had fluoropyrimidine-based therapy,with added cisplatin in 7 patients and epirubicin in 2 patients.Median recurrence-free survival was longer for the XRT group(52 mo) compared to the 5FU-RT(35 mo) and chemotherapy-only groups(25 mo)(P=0.48).The patients in the XRT group achieved similar median overall survival(53 mo) as the 5FU-RT(54 mo) and the chemotherapy-only groups(44 mo)(P=0.5).CONCLUSION:Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.
文摘Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates. To improve long-term outcomes, perioperative chemotherapies are combined with surgery. Human epidermal growth factor receptor 2 (HER2) overexpression had been noted in gastric cancer; therefore, trastuzumab has been used occasionally in this setting. A 63-year-old male Chinese patient, who was diagnosed with adenocarcinoma in the gastric antrum, as well as lymph node metastases along the left gastric and hepatic artery, and left adrenal area, was admitted to our hospital. HER2 expression was positive, and cluster amplification was detected in a fluorescence in situ hybridization assay. The patient received three cycles of a neoadjuvant trastuzumab/oxaliplatin /capecitabine regimen. He subsequently underwent distal gastrectomy, D2+ lymphadenectomy, left adrenalectomy, cholecystectomy and Billroth II anastomosis. Treatment was continued with another five postoperative cycles of the same medication and trastuzumab application for 1 year. No recurrence has been observed 18 mo after the operation. Trastuzumab as perioperative and adjuvant medication, in combination with oxaliplatin and capecitabine for a HER2-overexpressing advanced gastric adenocarcinoma, led to recurrence-free survival of at least 18 mo after surgery.
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Capecitabine (Xeloda) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specif ic conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capecitabine with standard folinic acid (leucovorin, LV)-modulated intravenous 5-fluorouracil (5-FU) bolus regimens in patients with metastatic colorectal cancer. Moreover the efficacy of Capecitabine on metastatic colorectal cancer, either alone or in various combinations with other active drugs such as Irinotecan and Oxaliplatin was also assessed. Finally, neoadjuvant therapy con- sisting of Capecitabine plus radiation therapy, for locally advanced rectal cancer was analysed. This combination of chemotherapy and radiotherapy has a special role in tumor down staging and in sphincter preservation for lower rectal tumors. Comparative trials have shown that Capecitabine is at least equivalent to the standard LV-5-FU combination in relation to progression-free and overall survival whilst showing a better tolerability prof ile with a much lower incidence of stomatitis. It is now known that Capecitabine can be combined with other active drugs such as Irinotecan and Oxaliplatin. The combination of Oxaliplatin with Capecitabine represents a new standard of care for metastatic colorectal cancer. Combinating the Capecitabine-Oxaliplatin regimen with promising new biological drugs such as Bevacizumab seems to give a realistic prospect of further improvement in time to progression of metastatic disease. Moreover, preoperative chemo-radiation using oral capecitabine is better tolerated than bolus 5-FU and is more effective in the promotion of both down-staging and sphincter preservation in patients with locally advanced rectal cancer. Finally, the outcomes of recently published trials suggest that capecitabine seems to be more cost effective than other standard treatments for the management of patients with colorectal cancer.
文摘Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC) patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from first-line chemotherapy,patients with mCRC in our hospital received two different treatment strategies.Thirty-three patients in maintenance group were treated with capecitabine 1000 mg/m2 po bid d1-14,q21d.Fifty-two patients in non-maintenance group did not receive any further chemotherapy.Results:Patients in maintenance group and non-maintenance group both received FOLFOX,FOLFIRI and XELOX as first-line therapy.The median chemotherapy cycles the two groups received were the same(6 vs 6).The response rates of first-line chemotherapy were 33.3% in maintenance group and 32.7% in non-maintenance group.Patients in maintenance group received 3-9 cycles of capecitabine therapy(median cycle 4).29/33(87.9%) patients in maintenance group and 47/52(90.4%) in non-maintenance group received following second-line chemotherapy,and no patients underwent targeted therapy.The median survival time and TTP were 40.4 months(95%CI:24.2-56.6) and 9.0 months(95%CI:6.7-11.3) in maintenance group,as compared with 21.5 months(95%CI:14.9-28.0,P=0.015) and 6.5 months(95%CI:4.4-8.5,P=0.007) in non-maintenance group.No severe adverse event was observed in the capecitabine maintenance group.Conclusion:mCRC patients could benefit from capecitabine maintenance therapy by prolonging survival time and TTP.
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.
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.
文摘BACKGROUND Capecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer.The most frequently reported adverse events attributed to capecitabine include diarrhea,hyperbilirubinemia,and hand-foot syndrome(HFS).A number of cutaneous adverse events have been attributed to capecitabine,including Stevens-Johnson syndrome(SJS)as a rare and potentially life-threatening mucocutaneous condition.We report the first case involving concurrent SJS and HFS after capecitabine and lapatinib treatment.CASE SUMMARY A 70-year-old woman with a history of breast cancer treatment visited our hospital for evaluation of painful skin lesions.Six weeks earlier,she had been prescribed capecitabine plus lapatinib as treatment for metastatic breast cancer.She subsequently developed worsening erythema and bullae on her palms and soles,as well as reddish macules on her back and chest wall.Histopathological evaluation of the chest wall lesions revealed extensive eosinophilic epidermal necrosis and separation of the epidermis from the dermis.The capecitabine plus lapatinib treatment was discontinued immediately and treatment was started using systemic steroids.This treatment resolved most lesions,although the lesions on her palms and soles required Vaseline gauze dressings,which resulted in reepithelialization.Therefore,we determined that the patient had concurrent SJS and HFS.Although the dermatological problems resolved,the patient ultimately died because of multiple organ failure.CONCLUSION Oral capecitabine treatment carries a risk of both HFS and also life-threatening adverse cutaneous drug reactions,such as SJS.
