Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide...Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide-functionalized prodrugs is a common in situ macromolecular prodrug strategy.However,the resulting reversible adducts are susceptible to retro-Michael reactions in vivo,leading to premature drug release and off-target effects.To address this limitation,a gemcitabine prodrug(GAB)bearing a chloroacetamide group was designed to form irreversible covalent bonds with albumin via nucleophilic substitution.A maleimide-based prodrug(GAM)was synthesized as a control.Compared to GAM,GAB showed faster and stronger albumin binding in plasma,enhanced blood circulation time,improved tumor accumulation,and superior in vivo antitumor efficacy.Moreover,GAB exhibited a better safety profile,with reduced cytotoxicity in normal tissues and no observable systemic toxicity.These advantages are attributed to the stable albumin-drug conjugate formed by GAB,which improves drug retention and targeted delivery.This study presents an effective and generalizable albumin-hitchhiking strategy for constructing irreversible prodrugs,offering a promising approach to enhance the therapeutic index of chemotherapeutic agents.展开更多
BACKGROUND Intrahepatic cholangiocarcinoma(iCCA)is the second most common liver malignancy with poor prognosis and limited treatment options.AIM To identify the most effective drug for transarterial chemoembolization(...BACKGROUND Intrahepatic cholangiocarcinoma(iCCA)is the second most common liver malignancy with poor prognosis and limited treatment options.AIM To identify the most effective drug for transarterial chemoembolization(TACE)in cholangiocarcinoma and evaluate the efficacy and safety of combining it with gemcitabine and cisplatin(GemCis)for unresectable iCCA.METHODS Cholangiocarcinoma cell lines(RBE,HuCC-T1)were treated with 10 chemotherapeutic drugs,and cytotoxicity was assessed by cell counting kit-8 assays.Tumorbearing nude mice were treated with idarubicin or GemCis,and tumor growth was monitored.Clinical data from 85 iCCA patients were analyzed to evaluate the efficacy and safety of idarubicin-TACE combined with GemCis.RESULTS Idarubicin demonstrated the highest cytotoxicity,significantly outperforming GemCis,the standard first-line therapies.In tumor-bearing mouse models,idarubicin and GemCis treatments significantly slowed tumor growth,with idarubicin showing particularly pronounced effects on days 12 and 15(P<0.05).In retrospective analysis,the median overall survival(OS)and progression-free survival(PFS)in the combination therapy group were significantly longer than those in the GemCis alone group(median OS,16.23 months vs 10.07 months,P=0.042;median PFS,7.73 months vs 6.30 months,P=0.023).Additionally,major grade 3/4 adverse events(AEs)in the combination therapy group were abdominal pain(26.3%vs 6.5%,P=0.049)and elevated transaminases(42.1%vs 12.9%,P=0.038).Most AEs were mild to moderate and manageable.CONCLUSION Idarubicin demonstrated higher cytotoxicity than GemCis,significantly inhibiting tumor growth in tumor-bearing mouse models.Preliminary clinical results suggest that local idarubicin-TACE combined with GemCis may offer improved survival outcomes for iCCA patients with a manageable safety profile.展开更多
Cholangiocarcinoma(CCA)is an aggressive cancer originating from bile duct epithelium.Surgical resection remains the primary curative treatment for CCA.However,most CCA patients are diagnosed at an advanced stage,which...Cholangiocarcinoma(CCA)is an aggressive cancer originating from bile duct epithelium.Surgical resection remains the primary curative treatment for CCA.However,most CCA patients are diagnosed at an advanced stage,which limits the applicability of surgical resection.Gemcitabine is widely used as a first-line chemotherapeutic agent for unresectable CCA.Its efficacy is often compromised by the development of drug resistance,which leads to poor clinical outcomes and low survival rates of CCA patients.At present,the mechanisms underlying gemcitabine resistance in CCA remain unclear.This review aimed to comprehensively summarize the current knowledge on the molecular mechanisms underlying gemcitabine resistance in CCA and highlight emerging therapeutic strategies that may overcome this resistance.Gemcitabine resistance arises through multiple mechanisms,including reduced drug uptake and increased efflux,impaired drug activation,enhanced DNA repair,apoptosis evasion,aberrations in cellcycle progression,induction of epithelial–mesenchymal transition,metabolic reprogramming,alteration of tumor,and activation of oncogenic pathways contributes to gemcitabine resistance.A deeper understanding of gemcitabine resistance mechanisms highlights the need for combining gemcitabine with pathway-specific inhibitors,which hold promise for overcoming resistance and improving patient outcomes.展开更多
Objective:Radical nephroureterectomy(RNU)is considered the standard of care for patients with high-risk upper tract urothelial carcinoma.Current literature reveals a deficit in direct comparative studies evaluating th...Objective:Radical nephroureterectomy(RNU)is considered the standard of care for patients with high-risk upper tract urothelial carcinoma.Current literature reveals a deficit in direct comparative studies evaluating the efficacy of different chemotherapeutic agents administered in single postoperative instillation following RNU.The primary aim of this study was to compare the bladder recurrence(BR)rates between patients receiving a single instillation of mitomycin C(MMC)versus gemcitabine(Gem)after RNU.Methods:The ROBUUST(ROBotic surgery for Upper tract Urothelial cancer STudy)2.0 is an international,multicenter registry that aggregates data on patients who have undergone curative surgery for upper tract urothelial carcinoma across participating centers from January 2015 to December 2022.Data including primary baseline variables of the patients,characteristics of the tumors,surgical management,and definitive histopathological characterizations were collected and stratified based on the type of postoperative bladder instillation:MMC(the MMC group)and Gem(the Gem group).We selected variables correlated with our primary outcome to conduct a propensity-score match analysis.Results:One hundred patients in the MMC group were matched 1:1 with 100 patients in the Gem group.At 36 months of follow-up,30 patients in the MMC group and 39 patients in the Gem group experienced BR,representing recurrence rates of 30%and 39%,respectively(p=0.2).The Cox proportional hazards model comparing BR between the groups revealed a hazard ratio of 1.58(95%confidence interval:0.98-2.55)with a non-statistically significant increased risk of BR in the Gem group compared with the MMC group(p=0.059).Conclusion:A single perioperative instillation of Gem or MMC seems to offer similar efficacy in reducing the risk of BR in patients undergoing RNU.Further research,ideally within the framework of prospective studies,is warranted to elucidate the optimal chemotherapeutic approach in this setting.展开更多
The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemc...The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunoche-motherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition;prolong chemotherapeutic plasma half-life (reduces administration frequency);minimize innocent exposure of normal tissues and healthy organ systems;and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunoche-motherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between?gemcitabine-equivalent concentrations of 10-12 M and 10-6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunoche-motherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] all had anti-neoplastic cytotoxic potency against mammary adenocarcinoma. Gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] produced progressive increases in anti-neoplastic cytotoxicity that were greatest between gemcitabine-equivalent concentrations of 10-9 M and 10-6 M. Dual simultaneous combinations of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] produced levels of anti-neoplastic cytotoxicity intermediate between each of the individual covalent gemcitabine immunochemotherapeutics. Total anti-neoplastic cytotoxicity of the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] against chemothe-rapeutic-resistant mammary adenocarcinoma (SKBr-3) was substantially higher when formulated with [Se]-methylsele-no-cysteine.展开更多
Objective： To evaluate the curative effectiveness of postoperative after-loading radiotherapy with the use of gemcitabine in 22 patients with primary liver cancer. Methods： From Oct. 1999 to Dec. 2001, 22 patients w...Objective： To evaluate the curative effectiveness of postoperative after-loading radiotherapy with the use of gemcitabine in 22 patients with primary liver cancer. Methods： From Oct. 1999 to Dec. 2001, 22 patients with primary liver cancer underwent postoperative after-loading radiotherapy 3-10 days after hepatectomy and chemotherapy using gemcitabine （1400 mg every week for 3 weeks, repeated after one week interval, total cycles were 6） and compared with 22 cases of sole hepatectomy. Three-six catheters were placed for irradiation after hepatectomy. The single-dose of after-loading radiotherapy was 10 Gy, 24 sessions per person. Results＇. The rate of AFP negative-reversion was 100% （17/17） in the treated group, higher than in control group （62.5%, 10/16, P〈0.05）. In the treated group, the 1-year relapse rate, metastasis rate and survival rate were 18.2% （4/22）, 0 and 100% （22/22） respectively, while in the control group they were 45.5% （10/22）, 13.6% （3/22） and 77.3% （17/22） respectively. There were significant differences between the two groups in relapse rate, metastasis rate and survival rate within a year （P〈0.05）. Conclusion： Postoperative after-loading radiotherapy with gemcitabine is an effective way for the treatment of primary liver cancer.展开更多
To evaluate the efficacy and safety of gemcitabine （GEM） at 30 min standard-dose infusion （30 min-SDI） compared with prolonged low-dose infusion （P-LDI） in patients with advanced non-small-cell lung cancer （NS...To evaluate the efficacy and safety of gemcitabine （GEM） at 30 min standard-dose infusion （30 min-SDI） compared with prolonged low-dose infusion （P-LDI） in patients with advanced non-small-cell lung cancer （NSCLC）. Electronic databases including Pubmed, EMbase, Cochrane Library, CNKI, CBM, and VIP were searched using keywords ＂GEM＂, ＂P-LDI＂, and ＂NSCLC＂. Review Manager 5.3 was used to perform the recta-analysis. Primary endpoints were overall response rate （ORR） and 1-year survival rate （1-year SR）. Secondary endpoints were grade 3/4 hematotoxicity and nausea/vomiting. Six randomized controlled trials （RCTs） with a total of 637 patients were included. The results showed that P-LDI was superior in ORR （OR = 1.50, 95% CI： 1.08-2.10, P = 0.02）, but had an equal 1-year SR （OR = 1.27, 95 % CI： 0.90-1.79, P = 0.18） as compared with 30 min-SDl. For grade 3/4 adverse events, there was no significant difference in anemia （OR = 1.84, 95% CI： 0.61-5.57, P = 0.28） and nausea/vomiting （OR = 1.15, 95% CI： 0.63-2.12, P = 0.64） between the two treatments. However, patients with P-LDI experienced less leukopenia （OR = 0.64, 95% CI： 0.43-0.97, P = 0.04） and thrombocytopenia （OR = 0.37, 95% CI： 0.17-0.80, P = 0.01）. P-LDI was superior in terms of ORR, experienced less grade 3/4 thrombocytopenia and leukopenia compared with 30 min-SDI, and could be a viable treatment option for advanced NSCLC.展开更多
Objective: To study the role of 125 I and 125 I plus gemcitabine (GEM) in treatment of unresectable carcinoma of pancreas. Methods: From April 2000 to April 2003, 38 untreated patients with locally advanced pan...Objective: To study the role of 125 I and 125 I plus gemcitabine (GEM) in treatment of unresectable carcinoma of pancreas. Methods: From April 2000 to April 2003, 38 untreated patients with locally advanced pancreatic cancer (LAPC) were collected and randomized into two groups: Arm A 125 I (18 patients) and Arm B 125 I+GEM (20 patients). Eligibility criteria were: cytologically and pathologically proven pancreatic carcinoma, Karnofsky performance status (kps) 60 80, age 18 75 years, adequate hematological, renal and liver function, and controllable pain. Arm A patients were treated with 125 I implants. Arm B patients started chemotherapy within 10 14 d post operatively following the implant procedure. Chemotherapy doses were as follows: GEM 1 000 mg/m 2 weekly × 3 followed by 1 week of rest for 3 cycles. In addition, all patients underwent laparotomy and surgical staging. The surgical procedures performed were biopsy, gastric bypass and biliary bypass. The total activity and number of seeds used were as recommended by Anderson. The mean activity, minimal peripheral dose (MPD), and volume of implants were 20 mCi, 14 000 cGy, and 53 cm 3, respectively. Results: Overall response rate (CR+PR) in Arm A was 37.6% and in Arm B it was 44.5% ( P >0.05). PR median duration in Arm A was 6.7 months and in Arm B it was 4.8 months ( P <0.05). Clinical benefit response was experienced by 11.7 % of Arm A compared with 42.1% of Arm B ( P <0.05). The incidences of hematological toxicity (such as neutropenia) between Arm A and Arm B were 5.8% and 21.1%, respectively ( P >0.05). The survival rates of 12 and 24 month were 32.5%, 16.3% for Arm A and 61%, 38.7% for Arm B ( P =0.04). The rate of complication of Arm A was lower than that of Arm B without statistical significance. Conclusion: To some extent, 125 I or 125 I plus GEM is able to lead to a moderate objective response for LAPC with obstructive jaundice on the base of biliary bypass or/and gastric bypass, but 125 I plus GEM is more effective than 125 I in improvement of the quality of life and survival rate in patients with LAPC.展开更多
Gambogic acid(GA) is a natural substance with a good antitumor effect, but it is too lipophilic to be metabolized and excreted, thus accumulating in the body. Gemcitabine(GEM), one of the first-line antitumor drugs, h...Gambogic acid(GA) is a natural substance with a good antitumor effect, but it is too lipophilic to be metabolized and excreted, thus accumulating in the body. Gemcitabine(GEM), one of the first-line antitumor drugs, has high hydrophilicity, which greatly shortens its half-life in vivo. We previously reported a compound named N-gamboyl gemcitabine(GAG), derived from the condensation of GEM and GA, whose hydrophilicity is better than GA and stability is better than GEM. Here, the antitumor performance of GAG was investigated for the first time by using several common tumor cell lines as tumor models. The results of in vitro study showed that GAG significantly inhibited the proliferation and migration of the tumor cells. The IC50 values of GAG for the tumor cells were lower than those of GEM and GA. The present study suggests that GAG has a promising potential to be developed into a broad-spectrum antitumor drug.展开更多
AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to...AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to assess the quality of life (QOL) of such patients. METHODS: Twenty-fi ve patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine (1000 mg/m2) over 30 min on days 1 and 8, 2 h infusion of oxaliplatin (120 mg/m2) on day 1, and 2-3 h infusion of huachansu (20 mL/m2) on days -3-11, every 3-4 wk. Treatment was continued until occurrence of unacceptable toxicity or disease progression. QOL of patients was assessed by the EORTC QLQ-C30 at baseline, at the end of the fi rst, third and sixth chemotherapy cycles, and 1 mo after the treatment. RESULTS: Among the 25 patients with a median age of 64 years (range 42-78 years), 23 were evaluable in the study. A total of 137 cycles of therapy were performed and the median cycle was 5 (range 1-8) per patient. Out of the 23 patients whose response couldbe evaluated, 8 partial responses (PR) were observed (34.8%), while 7 patients (30.4%) demonstrated a stable disease (SD). The disease control rate was 65.2%. Progression of cancer was observed in 8 (34.8%) patients. The median progression-free and overall survival time was 5.8 mo (95% CI: 4.5-7.1 mo) and 10.5 mo, respectively. The therapy was well tolerated, with moderate myelosuppression as the main toxicity. Anemia grade 2 was seen in 16.0%, neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients, respectively. Non-hematologic toxicity ranged from mild to moderate. No death occurred due to toxicity. The QOL of patients was improved after chemotherapy, and the scores of QOL were increased by 10 to 20 points. CONCLUSION: GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC.展开更多
AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undert...AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer.Inclusion was limited to highquality randomized clinical trials.RESULTS:Twenty-six studies were included in the present analysis,with a total of 8808 patients recruited.The studies were divided into four subgroups based on the different kinds of cytotoxic agents,including platinum,fluoropyrimidine,camptothecin and targeted agents.Patients treated with gemcitabine monotherapy had significantly lower objective response rate [risk ratio(RR),0.72;95% confidence interval(CI):0.63-0.83;P < 0.001],and lower 1-year overall survival(RR,0.90;95%CI:0.82-0.99;P = 0.04).Gemcitabine monotherapy caused fewer complications,including fewer grade 3-4 toxicities:including vomiting(RR,0.75;95%CI:0.62-0.89;P = 0.001),diarrhea(RR,0.66;95%CI:0.49-0.89;P = 0.006),neutropenia(RR,0.88;95%CI:0.72-1.06;P = 0.18),anemia(RR,0.96;95%CI:0.82-1.12;P = 0.60),and thrombocytopenia(RR,0.76;95%CI:0.60-0.97;P = 0.03) compared with gemcitabine combination therapies.CONCLUSION:Gemcitabine combination therapy provides a modest improvement of survival,but is associated with more toxicity compared with gemcitabine monotherapy.展开更多
Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two pa...Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.展开更多
Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advance...Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.展开更多
AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta- analysis. METHODS: MEDLINE and EMBASE searches were supplemented by in...AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta- analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-based combination therapy and GEM alone for APCa. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The meta-analysis involved overall survival (OS), objective remission rate (ORR), clinical benefit rate (CBR), time to progress/progress free survival (TTP/PFS) and toxicity. RESULTS: The meta-analysis included 22 RCTs. There was significant improvement in the GEM combination group with regard to the 6-mo survival rate (RD = 0.04, 95% CI 0.01-0.06, P = 0.008), 1-year survival rate (RD = 0.03, 95% CI 0.01-0.05, P = 0.01), ORR (RD = 0.04, 95% CI 0.01-0.07, P = 0.02), CBR (RD = 0.10, 95% CI 0.02-0.17, P = 0.01) and 6-mo TTP/PFS (RD = 0.07, 95% CI 0.04-0.10, P < 0.00001). However, the Grade 3-4 toxicity set by WHO was higher for the GEM combination group for neutropenia (RD = 0.05, 95% CI 0.01-0.10, P = 0.02), thrombocytopenia (RD = 0.05, 95% CI 0.02-0.08, P = 0.002) and vomiting/nausea (RD = 0.03, 95% CI 0.00-0.05, P = 0.02). CONCLUSION: GEM-based combination therapy may improve the overall survival and palliation in optimalpatients with APCa as compared with GEM alone.展开更多
AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1...AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group （without treatment）, photosensitizer treatment group （2 mg/kg photosan, without illumination）, chemotherapy group （50 mg/kg gemcitabine i.p.）, PDT group （2 mg/kg photosan ＋ laser irradiation） and combined treatment group （photosan ＋ chemotherapy）, with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition （TGI）RESULTS： No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy （0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25± 0.09, P 〈 0.05）. PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group （0.12 ± 0.07-0.28 ± 0.22 vs 0.39 ± 0.15-2.20 ± 0.12, P 〈 0.05）, small dose chemotherapy group （0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P 〈 0.05） and control group （0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P 〈 0.05）. TGI was higher in the combined treatment group （82.42%） than in the PDT group （58.18%）.CONCLUSION： PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.展开更多
AIM:To investigate the effect of propofol on human pancreatic cells and the molecular mechanism of propofol action.METHODS:We used the human pancreatic cancer cell line MIAPaCa-2 for in vitro studies measuring growth ...AIM:To investigate the effect of propofol on human pancreatic cells and the molecular mechanism of propofol action.METHODS:We used the human pancreatic cancer cell line MIAPaCa-2 for in vitro studies measuring growth inhibition and degree of apoptotic cell death induced by propofol alone,gemcitabine alone,or propofol followed by gemcitabine.All experiments were conducted in triplicate and carried out on three or more separate occasions.Data were means of the three or more independent experiments±SE.Statistically significant differences were determined by two-tailed unpaired Student’s t test and defined as P<0.05.RESULTS:Pretreatment of cells with propofol for 24 h followed by gemcitabine resulted in 24%-75% growth inhibition compared with 6%-18%when gemcitabine was used alone.Overall growth inhibition was directly correlated with apoptotic cell death.We also showed that propofol potentiated gemcitabine-induced killing by downregulation of nuclear factor-κB(NF-κB).In contrast,NF-κB was upregulated when pancreatic cancer cells were exposed to gemcitabine alone,suggesting a potential mechanism of acquired chemoresistance.CONCLUSION:Inactivation of the NF-κB signaling pathway by propofol might abrogate gemcitabineinduced activation of NF-κB,resulting in chemosensitization of pancreatic tumors to gemcitabine.展开更多
High human equilibrative nucleoside transporter 1(hENT1)-expression has shown a survival benefit in pancreatic cancer patients treated with gemcitabine in several studies.The aim of this systematic review was to summa...High human equilibrative nucleoside transporter 1(hENT1)-expression has shown a survival benefit in pancreatic cancer patients treated with gemcitabine in several studies.The aim of this systematic review was to summarize the results and try to assess the predictive value of hENT1 for determining gemcitabine outcome in pancreatic cancer.Relevant articles were obtained from PubMed,Embase and Cochrane databases.Studies evaluating hENT1-expression in pancreatic tumor cells from patients treated with gemcitabine were selected.Outcome measures were overall survival,disease-free survival(DFS),toxicity and response rate.The database searches identified 10 studies that met the eligibility criteria,and a total of 855 patients were included.Nine of 10 studies showed a statistically significant longer overall survival in univariate analyses in patients with high hENT1-expression compared to those with low expression.In the 7 studies that reported DFS as an outcome measure,6 had statistically longer DFS in the high hENT1 groups.Both toxicity and response rate were reported in only 2 articles and it was therefore hard to draw any major conclusions.This review provides evidence that hENT1 is a predictive marker for pancreatic cancer patients treated with gemcitabine.Some limitations of the review have to be taken into consideration,the majority of the included studies had a retrospective design,and there was no standardized scoring protocol for hENT1-expression.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82372115,52073139 and 82404553)the Postdoctoral Fellowship Program of Chinese Postdoctoral Science Foundation(No.GZC20231085).
文摘Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide-functionalized prodrugs is a common in situ macromolecular prodrug strategy.However,the resulting reversible adducts are susceptible to retro-Michael reactions in vivo,leading to premature drug release and off-target effects.To address this limitation,a gemcitabine prodrug(GAB)bearing a chloroacetamide group was designed to form irreversible covalent bonds with albumin via nucleophilic substitution.A maleimide-based prodrug(GAM)was synthesized as a control.Compared to GAM,GAB showed faster and stronger albumin binding in plasma,enhanced blood circulation time,improved tumor accumulation,and superior in vivo antitumor efficacy.Moreover,GAB exhibited a better safety profile,with reduced cytotoxicity in normal tissues and no observable systemic toxicity.These advantages are attributed to the stable albumin-drug conjugate formed by GAB,which improves drug retention and targeted delivery.This study presents an effective and generalizable albumin-hitchhiking strategy for constructing irreversible prodrugs,offering a promising approach to enhance the therapeutic index of chemotherapeutic agents.
基金Supported by the Guangzhou Science and Technology Plan Project,No.2023A04J0419National Natural Science Foundation Cultivation Project at the Third Affiliated Hospital of Sun Yat-sen University,No.2022GZRPYQN04.
文摘BACKGROUND Intrahepatic cholangiocarcinoma(iCCA)is the second most common liver malignancy with poor prognosis and limited treatment options.AIM To identify the most effective drug for transarterial chemoembolization(TACE)in cholangiocarcinoma and evaluate the efficacy and safety of combining it with gemcitabine and cisplatin(GemCis)for unresectable iCCA.METHODS Cholangiocarcinoma cell lines(RBE,HuCC-T1)were treated with 10 chemotherapeutic drugs,and cytotoxicity was assessed by cell counting kit-8 assays.Tumorbearing nude mice were treated with idarubicin or GemCis,and tumor growth was monitored.Clinical data from 85 iCCA patients were analyzed to evaluate the efficacy and safety of idarubicin-TACE combined with GemCis.RESULTS Idarubicin demonstrated the highest cytotoxicity,significantly outperforming GemCis,the standard first-line therapies.In tumor-bearing mouse models,idarubicin and GemCis treatments significantly slowed tumor growth,with idarubicin showing particularly pronounced effects on days 12 and 15(P<0.05).In retrospective analysis,the median overall survival(OS)and progression-free survival(PFS)in the combination therapy group were significantly longer than those in the GemCis alone group(median OS,16.23 months vs 10.07 months,P=0.042;median PFS,7.73 months vs 6.30 months,P=0.023).Additionally,major grade 3/4 adverse events(AEs)in the combination therapy group were abdominal pain(26.3%vs 6.5%,P=0.049)and elevated transaminases(42.1%vs 12.9%,P=0.038).Most AEs were mild to moderate and manageable.CONCLUSION Idarubicin demonstrated higher cytotoxicity than GemCis,significantly inhibiting tumor growth in tumor-bearing mouse models.Preliminary clinical results suggest that local idarubicin-TACE combined with GemCis may offer improved survival outcomes for iCCA patients with a manageable safety profile.
基金supported by the Khon Kaen University Graduate School.Funding was provided to W.Seubwai and S.Kidoikhammouan by the program to admit high potential students for study and research at the Graduate School[631JH219].
文摘Cholangiocarcinoma(CCA)is an aggressive cancer originating from bile duct epithelium.Surgical resection remains the primary curative treatment for CCA.However,most CCA patients are diagnosed at an advanced stage,which limits the applicability of surgical resection.Gemcitabine is widely used as a first-line chemotherapeutic agent for unresectable CCA.Its efficacy is often compromised by the development of drug resistance,which leads to poor clinical outcomes and low survival rates of CCA patients.At present,the mechanisms underlying gemcitabine resistance in CCA remain unclear.This review aimed to comprehensively summarize the current knowledge on the molecular mechanisms underlying gemcitabine resistance in CCA and highlight emerging therapeutic strategies that may overcome this resistance.Gemcitabine resistance arises through multiple mechanisms,including reduced drug uptake and increased efflux,impaired drug activation,enhanced DNA repair,apoptosis evasion,aberrations in cellcycle progression,induction of epithelial–mesenchymal transition,metabolic reprogramming,alteration of tumor,and activation of oncogenic pathways contributes to gemcitabine resistance.A deeper understanding of gemcitabine resistance mechanisms highlights the need for combining gemcitabine with pathway-specific inhibitors,which hold promise for overcoming resistance and improving patient outcomes.
文摘Objective:Radical nephroureterectomy(RNU)is considered the standard of care for patients with high-risk upper tract urothelial carcinoma.Current literature reveals a deficit in direct comparative studies evaluating the efficacy of different chemotherapeutic agents administered in single postoperative instillation following RNU.The primary aim of this study was to compare the bladder recurrence(BR)rates between patients receiving a single instillation of mitomycin C(MMC)versus gemcitabine(Gem)after RNU.Methods:The ROBUUST(ROBotic surgery for Upper tract Urothelial cancer STudy)2.0 is an international,multicenter registry that aggregates data on patients who have undergone curative surgery for upper tract urothelial carcinoma across participating centers from January 2015 to December 2022.Data including primary baseline variables of the patients,characteristics of the tumors,surgical management,and definitive histopathological characterizations were collected and stratified based on the type of postoperative bladder instillation:MMC(the MMC group)and Gem(the Gem group).We selected variables correlated with our primary outcome to conduct a propensity-score match analysis.Results:One hundred patients in the MMC group were matched 1:1 with 100 patients in the Gem group.At 36 months of follow-up,30 patients in the MMC group and 39 patients in the Gem group experienced BR,representing recurrence rates of 30%and 39%,respectively(p=0.2).The Cox proportional hazards model comparing BR between the groups revealed a hazard ratio of 1.58(95%confidence interval:0.98-2.55)with a non-statistically significant increased risk of BR in the Gem group compared with the MMC group(p=0.059).Conclusion:A single perioperative instillation of Gem or MMC seems to offer similar efficacy in reducing the risk of BR in patients undergoing RNU.Further research,ideally within the framework of prospective studies,is warranted to elucidate the optimal chemotherapeutic approach in this setting.
文摘The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunoche-motherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition;prolong chemotherapeutic plasma half-life (reduces administration frequency);minimize innocent exposure of normal tissues and healthy organ systems;and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunoche-motherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between?gemcitabine-equivalent concentrations of 10-12 M and 10-6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunoche-motherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] all had anti-neoplastic cytotoxic potency against mammary adenocarcinoma. Gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] produced progressive increases in anti-neoplastic cytotoxicity that were greatest between gemcitabine-equivalent concentrations of 10-9 M and 10-6 M. Dual simultaneous combinations of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] produced levels of anti-neoplastic cytotoxicity intermediate between each of the individual covalent gemcitabine immunochemotherapeutics. Total anti-neoplastic cytotoxicity of the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] against chemothe-rapeutic-resistant mammary adenocarcinoma (SKBr-3) was substantially higher when formulated with [Se]-methylsele-no-cysteine.
文摘Objective： To evaluate the curative effectiveness of postoperative after-loading radiotherapy with the use of gemcitabine in 22 patients with primary liver cancer. Methods： From Oct. 1999 to Dec. 2001, 22 patients with primary liver cancer underwent postoperative after-loading radiotherapy 3-10 days after hepatectomy and chemotherapy using gemcitabine （1400 mg every week for 3 weeks, repeated after one week interval, total cycles were 6） and compared with 22 cases of sole hepatectomy. Three-six catheters were placed for irradiation after hepatectomy. The single-dose of after-loading radiotherapy was 10 Gy, 24 sessions per person. Results＇. The rate of AFP negative-reversion was 100% （17/17） in the treated group, higher than in control group （62.5%, 10/16, P〈0.05）. In the treated group, the 1-year relapse rate, metastasis rate and survival rate were 18.2% （4/22）, 0 and 100% （22/22） respectively, while in the control group they were 45.5% （10/22）, 13.6% （3/22） and 77.3% （17/22） respectively. There were significant differences between the two groups in relapse rate, metastasis rate and survival rate within a year （P〈0.05）. Conclusion： Postoperative after-loading radiotherapy with gemcitabine is an effective way for the treatment of primary liver cancer.
文摘To evaluate the efficacy and safety of gemcitabine （GEM） at 30 min standard-dose infusion （30 min-SDI） compared with prolonged low-dose infusion （P-LDI） in patients with advanced non-small-cell lung cancer （NSCLC）. Electronic databases including Pubmed, EMbase, Cochrane Library, CNKI, CBM, and VIP were searched using keywords ＂GEM＂, ＂P-LDI＂, and ＂NSCLC＂. Review Manager 5.3 was used to perform the recta-analysis. Primary endpoints were overall response rate （ORR） and 1-year survival rate （1-year SR）. Secondary endpoints were grade 3/4 hematotoxicity and nausea/vomiting. Six randomized controlled trials （RCTs） with a total of 637 patients were included. The results showed that P-LDI was superior in ORR （OR = 1.50, 95% CI： 1.08-2.10, P = 0.02）, but had an equal 1-year SR （OR = 1.27, 95 % CI： 0.90-1.79, P = 0.18） as compared with 30 min-SDl. For grade 3/4 adverse events, there was no significant difference in anemia （OR = 1.84, 95% CI： 0.61-5.57, P = 0.28） and nausea/vomiting （OR = 1.15, 95% CI： 0.63-2.12, P = 0.64） between the two treatments. However, patients with P-LDI experienced less leukopenia （OR = 0.64, 95% CI： 0.43-0.97, P = 0.04） and thrombocytopenia （OR = 0.37, 95% CI： 0.17-0.80, P = 0.01）. P-LDI was superior in terms of ORR, experienced less grade 3/4 thrombocytopenia and leukopenia compared with 30 min-SDI, and could be a viable treatment option for advanced NSCLC.
文摘Objective: To study the role of 125 I and 125 I plus gemcitabine (GEM) in treatment of unresectable carcinoma of pancreas. Methods: From April 2000 to April 2003, 38 untreated patients with locally advanced pancreatic cancer (LAPC) were collected and randomized into two groups: Arm A 125 I (18 patients) and Arm B 125 I+GEM (20 patients). Eligibility criteria were: cytologically and pathologically proven pancreatic carcinoma, Karnofsky performance status (kps) 60 80, age 18 75 years, adequate hematological, renal and liver function, and controllable pain. Arm A patients were treated with 125 I implants. Arm B patients started chemotherapy within 10 14 d post operatively following the implant procedure. Chemotherapy doses were as follows: GEM 1 000 mg/m 2 weekly × 3 followed by 1 week of rest for 3 cycles. In addition, all patients underwent laparotomy and surgical staging. The surgical procedures performed were biopsy, gastric bypass and biliary bypass. The total activity and number of seeds used were as recommended by Anderson. The mean activity, minimal peripheral dose (MPD), and volume of implants were 20 mCi, 14 000 cGy, and 53 cm 3, respectively. Results: Overall response rate (CR+PR) in Arm A was 37.6% and in Arm B it was 44.5% ( P >0.05). PR median duration in Arm A was 6.7 months and in Arm B it was 4.8 months ( P <0.05). Clinical benefit response was experienced by 11.7 % of Arm A compared with 42.1% of Arm B ( P <0.05). The incidences of hematological toxicity (such as neutropenia) between Arm A and Arm B were 5.8% and 21.1%, respectively ( P >0.05). The survival rates of 12 and 24 month were 32.5%, 16.3% for Arm A and 61%, 38.7% for Arm B ( P =0.04). The rate of complication of Arm A was lower than that of Arm B without statistical significance. Conclusion: To some extent, 125 I or 125 I plus GEM is able to lead to a moderate objective response for LAPC with obstructive jaundice on the base of biliary bypass or/and gastric bypass, but 125 I plus GEM is more effective than 125 I in improvement of the quality of life and survival rate in patients with LAPC.
基金Science&Technology Commission of Shanghai MunicipalityChina (No.20DZ2254900)+3 种基金Municipal Public Welfare Research Project from JiaxingZhejiang ProvinceChina (No.2022AY10001)Open Project Program of Jiaxing Key Laboratory of Virus-Related Infectious Diseases。
文摘Gambogic acid(GA) is a natural substance with a good antitumor effect, but it is too lipophilic to be metabolized and excreted, thus accumulating in the body. Gemcitabine(GEM), one of the first-line antitumor drugs, has high hydrophilicity, which greatly shortens its half-life in vivo. We previously reported a compound named N-gamboyl gemcitabine(GAG), derived from the condensation of GEM and GA, whose hydrophilicity is better than GA and stability is better than GEM. Here, the antitumor performance of GAG was investigated for the first time by using several common tumor cell lines as tumor models. The results of in vitro study showed that GAG significantly inhibited the proliferation and migration of the tumor cells. The IC50 values of GAG for the tumor cells were lower than those of GEM and GA. The present study suggests that GAG has a promising potential to be developed into a broad-spectrum antitumor drug.
文摘AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to assess the quality of life (QOL) of such patients. METHODS: Twenty-fi ve patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine (1000 mg/m2) over 30 min on days 1 and 8, 2 h infusion of oxaliplatin (120 mg/m2) on day 1, and 2-3 h infusion of huachansu (20 mL/m2) on days -3-11, every 3-4 wk. Treatment was continued until occurrence of unacceptable toxicity or disease progression. QOL of patients was assessed by the EORTC QLQ-C30 at baseline, at the end of the fi rst, third and sixth chemotherapy cycles, and 1 mo after the treatment. RESULTS: Among the 25 patients with a median age of 64 years (range 42-78 years), 23 were evaluable in the study. A total of 137 cycles of therapy were performed and the median cycle was 5 (range 1-8) per patient. Out of the 23 patients whose response couldbe evaluated, 8 partial responses (PR) were observed (34.8%), while 7 patients (30.4%) demonstrated a stable disease (SD). The disease control rate was 65.2%. Progression of cancer was observed in 8 (34.8%) patients. The median progression-free and overall survival time was 5.8 mo (95% CI: 4.5-7.1 mo) and 10.5 mo, respectively. The therapy was well tolerated, with moderate myelosuppression as the main toxicity. Anemia grade 2 was seen in 16.0%, neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients, respectively. Non-hematologic toxicity ranged from mild to moderate. No death occurred due to toxicity. The QOL of patients was improved after chemotherapy, and the scores of QOL were increased by 10 to 20 points. CONCLUSION: GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC.
文摘AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer.Inclusion was limited to highquality randomized clinical trials.RESULTS:Twenty-six studies were included in the present analysis,with a total of 8808 patients recruited.The studies were divided into four subgroups based on the different kinds of cytotoxic agents,including platinum,fluoropyrimidine,camptothecin and targeted agents.Patients treated with gemcitabine monotherapy had significantly lower objective response rate [risk ratio(RR),0.72;95% confidence interval(CI):0.63-0.83;P < 0.001],and lower 1-year overall survival(RR,0.90;95%CI:0.82-0.99;P = 0.04).Gemcitabine monotherapy caused fewer complications,including fewer grade 3-4 toxicities:including vomiting(RR,0.75;95%CI:0.62-0.89;P = 0.001),diarrhea(RR,0.66;95%CI:0.49-0.89;P = 0.006),neutropenia(RR,0.88;95%CI:0.72-1.06;P = 0.18),anemia(RR,0.96;95%CI:0.82-1.12;P = 0.60),and thrombocytopenia(RR,0.76;95%CI:0.60-0.97;P = 0.03) compared with gemcitabine combination therapies.CONCLUSION:Gemcitabine combination therapy provides a modest improvement of survival,but is associated with more toxicity compared with gemcitabine monotherapy.
文摘Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.
文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.
文摘AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta- analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-based combination therapy and GEM alone for APCa. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The meta-analysis involved overall survival (OS), objective remission rate (ORR), clinical benefit rate (CBR), time to progress/progress free survival (TTP/PFS) and toxicity. RESULTS: The meta-analysis included 22 RCTs. There was significant improvement in the GEM combination group with regard to the 6-mo survival rate (RD = 0.04, 95% CI 0.01-0.06, P = 0.008), 1-year survival rate (RD = 0.03, 95% CI 0.01-0.05, P = 0.01), ORR (RD = 0.04, 95% CI 0.01-0.07, P = 0.02), CBR (RD = 0.10, 95% CI 0.02-0.17, P = 0.01) and 6-mo TTP/PFS (RD = 0.07, 95% CI 0.04-0.10, P < 0.00001). However, the Grade 3-4 toxicity set by WHO was higher for the GEM combination group for neutropenia (RD = 0.05, 95% CI 0.01-0.10, P = 0.02), thrombocytopenia (RD = 0.05, 95% CI 0.02-0.08, P = 0.002) and vomiting/nausea (RD = 0.03, 95% CI 0.00-0.05, P = 0.02). CONCLUSION: GEM-based combination therapy may improve the overall survival and palliation in optimalpatients with APCa as compared with GEM alone.
文摘AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group （without treatment）, photosensitizer treatment group （2 mg/kg photosan, without illumination）, chemotherapy group （50 mg/kg gemcitabine i.p.）, PDT group （2 mg/kg photosan ＋ laser irradiation） and combined treatment group （photosan ＋ chemotherapy）, with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition （TGI）RESULTS： No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy （0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25± 0.09, P 〈 0.05）. PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group （0.12 ± 0.07-0.28 ± 0.22 vs 0.39 ± 0.15-2.20 ± 0.12, P 〈 0.05）, small dose chemotherapy group （0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P 〈 0.05） and control group （0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P 〈 0.05）. TGI was higher in the combined treatment group （82.42%） than in the PDT group （58.18%）.CONCLUSION： PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.
文摘AIM:To investigate the effect of propofol on human pancreatic cells and the molecular mechanism of propofol action.METHODS:We used the human pancreatic cancer cell line MIAPaCa-2 for in vitro studies measuring growth inhibition and degree of apoptotic cell death induced by propofol alone,gemcitabine alone,or propofol followed by gemcitabine.All experiments were conducted in triplicate and carried out on three or more separate occasions.Data were means of the three or more independent experiments±SE.Statistically significant differences were determined by two-tailed unpaired Student’s t test and defined as P<0.05.RESULTS:Pretreatment of cells with propofol for 24 h followed by gemcitabine resulted in 24%-75% growth inhibition compared with 6%-18%when gemcitabine was used alone.Overall growth inhibition was directly correlated with apoptotic cell death.We also showed that propofol potentiated gemcitabine-induced killing by downregulation of nuclear factor-κB(NF-κB).In contrast,NF-κB was upregulated when pancreatic cancer cells were exposed to gemcitabine alone,suggesting a potential mechanism of acquired chemoresistance.CONCLUSION:Inactivation of the NF-κB signaling pathway by propofol might abrogate gemcitabineinduced activation of NF-κB,resulting in chemosensitization of pancreatic tumors to gemcitabine.
文摘High human equilibrative nucleoside transporter 1(hENT1)-expression has shown a survival benefit in pancreatic cancer patients treated with gemcitabine in several studies.The aim of this systematic review was to summarize the results and try to assess the predictive value of hENT1 for determining gemcitabine outcome in pancreatic cancer.Relevant articles were obtained from PubMed,Embase and Cochrane databases.Studies evaluating hENT1-expression in pancreatic tumor cells from patients treated with gemcitabine were selected.Outcome measures were overall survival,disease-free survival(DFS),toxicity and response rate.The database searches identified 10 studies that met the eligibility criteria,and a total of 855 patients were included.Nine of 10 studies showed a statistically significant longer overall survival in univariate analyses in patients with high hENT1-expression compared to those with low expression.In the 7 studies that reported DFS as an outcome measure,6 had statistically longer DFS in the high hENT1 groups.Both toxicity and response rate were reported in only 2 articles and it was therefore hard to draw any major conclusions.This review provides evidence that hENT1 is a predictive marker for pancreatic cancer patients treated with gemcitabine.Some limitations of the review have to be taken into consideration,the majority of the included studies had a retrospective design,and there was no standardized scoring protocol for hENT1-expression.
