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
Objective: To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU (PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric juncti...Objective: To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU (PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction (EGJ) adenocarcinoma in China. Methods: The patients were treated with paclitaxel 150 mg/m2 on dl; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/(mLd) intravenously on d 1-d5 of a 21-d cycle until disease progression or unacceptable toxicities. Results: Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy (group A) and 34 received the regimen as the second-line therapy (group B) with the median age of 59 years old and Karnofsky performance status (KPS) score 〉80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival (mOS) was 12.0 months (95% CI: 7.9-16.2 months) in group A and 7.3 months (95% CI: 4.3-10.3 months) in group B, respectively. The median progression-free survival (mPFS) was 5.7 months (95% CI: 4.1-7.2 months) and 5.0 months (95% CI: 3.1-6.9 months), respectively. The response rate (CR^PR) was 40% (16/40; 95% CI: 24.9-56.7%) in group A and 22.6% (7/31; 95% CI: 9.6-41.1%) in group B. Major grade 3 or 4 adverse events include neutropenia (41.3 %), febrile neutropenia (9.3 %), nausea/anorexia (10.7%), and vomiting (5.3 %). There was no treatment-related death. Conclusions: The combination chemotherapy with PCF is active and tolerable as first-line and second- line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.展开更多
BACKGROUND As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil(DCF) and epirubicin, cisplatin, and 5-fluorouracil(ECF) regimens are commonly used in c...BACKGROUND As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil(DCF) and epirubicin, cisplatin, and 5-fluorouracil(ECF) regimens are commonly used in clinical practice, but there is still controversy about which is better.AIM To compare the efficacy and safety of DCF and ECF regimens by conducting this meta-analysis.METHODS Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival(PFS), overall survival(OS), objective response rate(ORR), disease control rate(DCR), and adverse effects(AEs) as endpoints for analysis.RESULTS Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS(95%CI: 0.58-1.46, P = 0.73), OS(95%CI: 0.65-1.10, P = 0.21),and total AEs(95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR(95%CI: 1.13-1.75, P = 0.002) and DCR(95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group(95%CI: 1.16-1.88, P = 0.002),especially for neutropenia and febrile neutropenia.CONCLUSION With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.展开更多
Chemotherapy with continuous infusion of 5-fluorouracil and cisplatin in a monthly schedule is one of the most common regimens in the treatment of advanced gastric cancer. In this study, we evaluated the efficacy and ...Chemotherapy with continuous infusion of 5-fluorouracil and cisplatin in a monthly schedule is one of the most common regimens in the treatment of advanced gastric cancer. In this study, we evaluated the efficacy and safety of a dosedense administration of this regimen in this patient population. Sixty-six consecutive patients with previously untreated histologically confirmed unresectable or metastatic gastric adenocarcinoma were treated with a 2-hour infusion of cisplatin 100 mg/m2 followed by continuous infusion of 5-fluorouracil 1000 mg/m2/day for 5 days, every 21 days. The most common grade ≥3 toxicities were fatigue (42%), nausea/vomiting (30%) and leucopenia (12%). Four patients (6%) died from treatment-related toxicity. The response rate was 35%, the median progression-free survival was 4.3 months and the median survival was 5.9 months. In light of these results, the dose-dense approach seems to offer little, if any, benefit compared with the standard regimens.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 the efficacy and safety of paclitaxel combined with fluorouracil plus cisplatin(PCF),and oxaliplatin combined with fluorouracil plus leucovorin(FOLFOX-4) regimens for advanced gastric cancer(AGC).METHOD...AIM:To compare the efficacy and safety of paclitaxel combined with fluorouracil plus cisplatin(PCF),and oxaliplatin combined with fluorouracil plus leucovorin(FOLFOX-4) regimens for advanced gastric cancer(AGC).METHODS:Ninety-four patients with AGC were randomly assigned to receive paclitaxel(50 mg/m2 iv) on days 1,8 and 15,cisplatin(20 mg/m2 iv) and ? uorouracil(750 mg/m2 iv) on days 1-5,or oxaliplatin(85 mg/m2 iv) and leucovorin(200 mg/m2 iv) on day 1,followed by bolus fluorouracil(400 mg/m2 iv) and fluorouracil(600 mg/m2 iv) on days 1 and 2.The primary end point was the 1-year survival time.RESULTS:The overall response rate(ORR) of the pa-tients was 48.0% and 45.5% to PCF and FOLFOX-4,respectively.The disease control rate(DCR) of PCF and FOLFOX-4 was 82.0% and 81.8%,respectively.The median survival times(MSTs) of the patients were 10.8 and 9.9 mo,respectively,after treatment with PCF and FOLFOX-4.The 1-year survival rate of the patients was 36.0% and 34.1%,respectively,after treatment with PCF and FOLFOX-4.No significant difference was observed in ORR,DCR,MST or 1-year survival rate between the two groups.The most common adverse events were anemia,nausea and vomiting,and grade 3/4 alopecia in PCF treatment group,and anemia,grade 1/2 neurotoxic effect and grade 3/4 neutropenia in FOLFOX-4 treatment group.CONCLUSION:Patients with AGC have a similar response rate to PCF and FOLFOX-4 regimens with a similar survival rate.The PCF and FOLFOX-4 regimens are efficacious and tolerable as a promising therapy for AGC.展开更多
BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the ...BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.展开更多
Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum antica...Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.展开更多
Objective: The aim of this study was to evaluate the efficacy and toxicity of modified docetaxel, cisplatin and calcium folinate (CF)/5-fluorouracil (mDCF) combination therapy for 27 patients with recurrent or metasta...Objective: The aim of this study was to evaluate the efficacy and toxicity of modified docetaxel, cisplatin and calcium folinate (CF)/5-fluorouracil (mDCF) combination therapy for 27 patients with recurrent or metastatic gastric adeno- carcinoma (R/MGC). Methods: From May 2006 to July 2007, 27 R/MGC patients (18 were male and 9 were female) with a median age of 49 years (range19-66) were consecutively enrolled. The mDCF protocol included 50 mg/m2 docetaxel for 1 day and 25 mg/m2 cisplatin on d2-3, 200 mg/m2 CF on d2-3 and 2000 mg/m2 5-fluorouracil (5-FU) CIV (continous infusion) for 46 h on d2-3, repeated every 2 weeks. Results: Twenty-seven patients were evaluable for efficacy and toxicity. A median of 4.5 cycles was given. One complete and 12 partial responses were observed for an overall intent to treat response rate (RR) 48.1% [95% CI (confidence intervals): 32%-64%]. Median time-to-progression (TTP) was 6.2 months and overall survival (OS) was 11.8 months. Twenty-seven (100%) patients experienced bone marrow suppression, and of them 48.9% were Grade 3-4 (16.3% were Grade 4). Two patients (7.4%) ceased chemotherapy because of bone marrow suppression. WHO Grade 1-4 non-hematological toxicity, such as oral mucositis, nausea/emesia, peripheral neuropathy, liver dysfunction, diarrhea, nephrotoxicity and cardiotoxicity, occurred in 59.2%、51.9%, 48.1%, 44.4%, 25.9%, 18.5% and 11.1% patients, respectively, and most of them were Grade 1-2. No patient died due to chemotherapy toxicity. Conclusion: mDCF regimen is effective in treating R/MGC with a high RR and long TTP/OS in this trial. Despite its severe hematotoxicity, this regimen has some advantages such as no cross-resistance with paclitaxel (paclitaxel-resistant patients RR 2/6). These results suggested that the mDCF regimen worth further investigation in clinical study of R/MGC treatment.展开更多
Background:?The role of chemotherapy in Gastric Cancer is constantly evolving?with various neoadjuvant and adjuvant strategies. Several chemotherapeutic agents are used in the treatment of locally advanced gastric can...Background:?The role of chemotherapy in Gastric Cancer is constantly evolving?with various neoadjuvant and adjuvant strategies. Several chemotherapeutic agents are used in the treatment of locally advanced gastric cancer (LAGC) namely Platinum based compounds (Cisplatin, Oxaliplatin), Fluoropyrimidines like 5-Flurouracil [(5-FU), Capecitabine)], Taxanes (Docetaxel) and Anthracyclines (Epirubicin). Various doublet and triplet combination chemotherapy regimens have been used for neo-adjuvant chemotherapy (NACT) in LAGCs. In this study we evaluated the safety and efficacy of docetaxel based triplet regimen DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] in LAGC. Material and methods:?50 Newly diagnosed patients of Locally Advanced Gastric Cancer (stage II or III) deemed fit to receive chemotherapy were included in our study. After 3 cycles of neoadjuvant chemotherapy, patients were assessed based on radiological and pathological response.?Results: 50 Patients were included in our study of which majority were male (32), median age at presentation was 55 years and 24 patients presented with a history of gastrointestinal reflux disease (GERD). The most common hematological toxicities observed in our study were anemia (61.2%), neutropenia (42.6%, febrile neutropenia constituted 6%) and thrombocytopenia (13.2%). The most common gastro-intestinal [GI] toxicities observed in our study included nausea (69.2%), vomiting (31.2%), diarrhea (34%), oral mucositis (14%) and constipation (6.6%). We found that safety profile of DOF regimen was favorable with majority of patients tolerating the regimen well. The Overall Response Rate (68%), Disease Control Rate (96%) and Resectability Rate (80%) were higher compared to western studies. Pathological CR (17.5%), ypN0?disease status (42.5%) and nodal down staging (52%), all showed positive correlations with survival outcomes. Conclusion:?DOF regimen is an effective and feasible option for neoadjuvant treatment of LAGC in an Indian population.展开更多
Objective:There remains no standard first-line chemotherapeutic regimen for advanced gastric cancer (AGC).The aim of this study was to evaluate the efficacy and safety of combination regimen with weekly paclitaxel and...Objective:There remains no standard first-line chemotherapeutic regimen for advanced gastric cancer (AGC).The aim of this study was to evaluate the efficacy and safety of combination regimen with weekly paclitaxel and S-1 as a first-line chemotherapy for AGC. Methods:Forty-six patients with AGC were included in this study. Paclitaxel was administered weekly at a dose of 60 mg/m2 on days 1, 8 and 15, S-1 was administered orally twice daily at 80 mg/m2/day for 2 weeks. The regimen was repeated every four weeks. Results:The results showed that the overall response rate was 45.7%, with 3 patients achieved complete response and 18 patients had a partial response, the disease control rate was 76.1%. The median progress free survival was 7.2 months 95% confidence interval (CI):6.3-8.1 months and the median overall survival was 11.6 months (95% CI:10.6-12.6 months) after treatment with paclitaxel and S-1. Neutropenia occurred in 25 patients (54.3%) and grade 3/4 neutropenia was observed in 8 patients (17.4%), gastrointestinal reactions were the most common non-hematologic toxicities, while severe gastrointestinal toxicities were uncommon. Conclusion:The regimen of weekly paclitaxel and S-1 demonstrated activity and acceptable toxicity for AGC as a first-line chemotherapy.展开更多
Objective:To analyze the effect of intraperitoneal administration of paclitaxel combined with cisplatin in treatment of advanced ovarian cancer.Method:Fifty-four patients with advanced ovarian cancer in our hospital w...Objective:To analyze the effect of intraperitoneal administration of paclitaxel combined with cisplatin in treatment of advanced ovarian cancer.Method:Fifty-four patients with advanced ovarian cancer in our hospital were randomly selected from the beginning of July 2018 to the end of June 2019.The principle of grouping was based on double-blind randomization method.In experimental group,27 patients were given intraperitoneal administration of paclitaxel combined with cisplatin.In control group,27 patients were given intravenous administration of paclitaxel combined with cisplatin.Clinical data of the two groups were compared.Results:Short-term clinical efficacy and T lymphocyte subsets of experimental group were significantly improved when compared with control group.The difference was significant(P<0.05).There was no significant difference in adverse reactions between the two groups(P>0.05).Conclusion:The effect of intraperitoneal administration of paclitaxel combined with cisplatin is ideal for treatment of advanced ovarian cancer patients.展开更多
AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 tre...AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.展开更多
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.
文摘Objective: To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU (PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction (EGJ) adenocarcinoma in China. Methods: The patients were treated with paclitaxel 150 mg/m2 on dl; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/(mLd) intravenously on d 1-d5 of a 21-d cycle until disease progression or unacceptable toxicities. Results: Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy (group A) and 34 received the regimen as the second-line therapy (group B) with the median age of 59 years old and Karnofsky performance status (KPS) score 〉80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival (mOS) was 12.0 months (95% CI: 7.9-16.2 months) in group A and 7.3 months (95% CI: 4.3-10.3 months) in group B, respectively. The median progression-free survival (mPFS) was 5.7 months (95% CI: 4.1-7.2 months) and 5.0 months (95% CI: 3.1-6.9 months), respectively. The response rate (CR^PR) was 40% (16/40; 95% CI: 24.9-56.7%) in group A and 22.6% (7/31; 95% CI: 9.6-41.1%) in group B. Major grade 3 or 4 adverse events include neutropenia (41.3 %), febrile neutropenia (9.3 %), nausea/anorexia (10.7%), and vomiting (5.3 %). There was no treatment-related death. Conclusions: The combination chemotherapy with PCF is active and tolerable as first-line and second- line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.
基金Supported by National Natural Science Foundation of China,No.81560345
文摘BACKGROUND As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil(DCF) and epirubicin, cisplatin, and 5-fluorouracil(ECF) regimens are commonly used in clinical practice, but there is still controversy about which is better.AIM To compare the efficacy and safety of DCF and ECF regimens by conducting this meta-analysis.METHODS Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival(PFS), overall survival(OS), objective response rate(ORR), disease control rate(DCR), and adverse effects(AEs) as endpoints for analysis.RESULTS Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS(95%CI: 0.58-1.46, P = 0.73), OS(95%CI: 0.65-1.10, P = 0.21),and total AEs(95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR(95%CI: 1.13-1.75, P = 0.002) and DCR(95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group(95%CI: 1.16-1.88, P = 0.002),especially for neutropenia and febrile neutropenia.CONCLUSION With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.
文摘Chemotherapy with continuous infusion of 5-fluorouracil and cisplatin in a monthly schedule is one of the most common regimens in the treatment of advanced gastric cancer. In this study, we evaluated the efficacy and safety of a dosedense administration of this regimen in this patient population. Sixty-six consecutive patients with previously untreated histologically confirmed unresectable or metastatic gastric adenocarcinoma were treated with a 2-hour infusion of cisplatin 100 mg/m2 followed by continuous infusion of 5-fluorouracil 1000 mg/m2/day for 5 days, every 21 days. The most common grade ≥3 toxicities were fatigue (42%), nausea/vomiting (30%) and leucopenia (12%). Four patients (6%) died from treatment-related toxicity. The response rate was 35%, the median progression-free survival was 4.3 months and the median survival was 5.9 months. In light of these results, the dose-dense approach seems to offer little, if any, benefit compared with the standard regimens.
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.
基金Supported by The National Natural Science Foundation of China, No. 30872176, 30950022 and 30972703Jiangsu Province of China, No. K200403Department of Public Health and Department of Science and Technology (BS2005616)
文摘AIM:To compare the efficacy and safety of paclitaxel combined with fluorouracil plus cisplatin(PCF),and oxaliplatin combined with fluorouracil plus leucovorin(FOLFOX-4) regimens for advanced gastric cancer(AGC).METHODS:Ninety-four patients with AGC were randomly assigned to receive paclitaxel(50 mg/m2 iv) on days 1,8 and 15,cisplatin(20 mg/m2 iv) and ? uorouracil(750 mg/m2 iv) on days 1-5,or oxaliplatin(85 mg/m2 iv) and leucovorin(200 mg/m2 iv) on day 1,followed by bolus fluorouracil(400 mg/m2 iv) and fluorouracil(600 mg/m2 iv) on days 1 and 2.The primary end point was the 1-year survival time.RESULTS:The overall response rate(ORR) of the pa-tients was 48.0% and 45.5% to PCF and FOLFOX-4,respectively.The disease control rate(DCR) of PCF and FOLFOX-4 was 82.0% and 81.8%,respectively.The median survival times(MSTs) of the patients were 10.8 and 9.9 mo,respectively,after treatment with PCF and FOLFOX-4.The 1-year survival rate of the patients was 36.0% and 34.1%,respectively,after treatment with PCF and FOLFOX-4.No significant difference was observed in ORR,DCR,MST or 1-year survival rate between the two groups.The most common adverse events were anemia,nausea and vomiting,and grade 3/4 alopecia in PCF treatment group,and anemia,grade 1/2 neurotoxic effect and grade 3/4 neutropenia in FOLFOX-4 treatment group.CONCLUSION:Patients with AGC have a similar response rate to PCF and FOLFOX-4 regimens with a similar survival rate.The PCF and FOLFOX-4 regimens are efficacious and tolerable as a promising therapy for AGC.
文摘BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.
基金Supported by Kyungpook National University Research Fund,2012
文摘Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.
文摘Objective: The aim of this study was to evaluate the efficacy and toxicity of modified docetaxel, cisplatin and calcium folinate (CF)/5-fluorouracil (mDCF) combination therapy for 27 patients with recurrent or metastatic gastric adeno- carcinoma (R/MGC). Methods: From May 2006 to July 2007, 27 R/MGC patients (18 were male and 9 were female) with a median age of 49 years (range19-66) were consecutively enrolled. The mDCF protocol included 50 mg/m2 docetaxel for 1 day and 25 mg/m2 cisplatin on d2-3, 200 mg/m2 CF on d2-3 and 2000 mg/m2 5-fluorouracil (5-FU) CIV (continous infusion) for 46 h on d2-3, repeated every 2 weeks. Results: Twenty-seven patients were evaluable for efficacy and toxicity. A median of 4.5 cycles was given. One complete and 12 partial responses were observed for an overall intent to treat response rate (RR) 48.1% [95% CI (confidence intervals): 32%-64%]. Median time-to-progression (TTP) was 6.2 months and overall survival (OS) was 11.8 months. Twenty-seven (100%) patients experienced bone marrow suppression, and of them 48.9% were Grade 3-4 (16.3% were Grade 4). Two patients (7.4%) ceased chemotherapy because of bone marrow suppression. WHO Grade 1-4 non-hematological toxicity, such as oral mucositis, nausea/emesia, peripheral neuropathy, liver dysfunction, diarrhea, nephrotoxicity and cardiotoxicity, occurred in 59.2%、51.9%, 48.1%, 44.4%, 25.9%, 18.5% and 11.1% patients, respectively, and most of them were Grade 1-2. No patient died due to chemotherapy toxicity. Conclusion: mDCF regimen is effective in treating R/MGC with a high RR and long TTP/OS in this trial. Despite its severe hematotoxicity, this regimen has some advantages such as no cross-resistance with paclitaxel (paclitaxel-resistant patients RR 2/6). These results suggested that the mDCF regimen worth further investigation in clinical study of R/MGC treatment.
文摘Background:?The role of chemotherapy in Gastric Cancer is constantly evolving?with various neoadjuvant and adjuvant strategies. Several chemotherapeutic agents are used in the treatment of locally advanced gastric cancer (LAGC) namely Platinum based compounds (Cisplatin, Oxaliplatin), Fluoropyrimidines like 5-Flurouracil [(5-FU), Capecitabine)], Taxanes (Docetaxel) and Anthracyclines (Epirubicin). Various doublet and triplet combination chemotherapy regimens have been used for neo-adjuvant chemotherapy (NACT) in LAGCs. In this study we evaluated the safety and efficacy of docetaxel based triplet regimen DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] in LAGC. Material and methods:?50 Newly diagnosed patients of Locally Advanced Gastric Cancer (stage II or III) deemed fit to receive chemotherapy were included in our study. After 3 cycles of neoadjuvant chemotherapy, patients were assessed based on radiological and pathological response.?Results: 50 Patients were included in our study of which majority were male (32), median age at presentation was 55 years and 24 patients presented with a history of gastrointestinal reflux disease (GERD). The most common hematological toxicities observed in our study were anemia (61.2%), neutropenia (42.6%, febrile neutropenia constituted 6%) and thrombocytopenia (13.2%). The most common gastro-intestinal [GI] toxicities observed in our study included nausea (69.2%), vomiting (31.2%), diarrhea (34%), oral mucositis (14%) and constipation (6.6%). We found that safety profile of DOF regimen was favorable with majority of patients tolerating the regimen well. The Overall Response Rate (68%), Disease Control Rate (96%) and Resectability Rate (80%) were higher compared to western studies. Pathological CR (17.5%), ypN0?disease status (42.5%) and nodal down staging (52%), all showed positive correlations with survival outcomes. Conclusion:?DOF regimen is an effective and feasible option for neoadjuvant treatment of LAGC in an Indian population.
文摘Objective:There remains no standard first-line chemotherapeutic regimen for advanced gastric cancer (AGC).The aim of this study was to evaluate the efficacy and safety of combination regimen with weekly paclitaxel and S-1 as a first-line chemotherapy for AGC. Methods:Forty-six patients with AGC were included in this study. Paclitaxel was administered weekly at a dose of 60 mg/m2 on days 1, 8 and 15, S-1 was administered orally twice daily at 80 mg/m2/day for 2 weeks. The regimen was repeated every four weeks. Results:The results showed that the overall response rate was 45.7%, with 3 patients achieved complete response and 18 patients had a partial response, the disease control rate was 76.1%. The median progress free survival was 7.2 months 95% confidence interval (CI):6.3-8.1 months and the median overall survival was 11.6 months (95% CI:10.6-12.6 months) after treatment with paclitaxel and S-1. Neutropenia occurred in 25 patients (54.3%) and grade 3/4 neutropenia was observed in 8 patients (17.4%), gastrointestinal reactions were the most common non-hematologic toxicities, while severe gastrointestinal toxicities were uncommon. Conclusion:The regimen of weekly paclitaxel and S-1 demonstrated activity and acceptable toxicity for AGC as a first-line chemotherapy.
文摘Objective:To analyze the effect of intraperitoneal administration of paclitaxel combined with cisplatin in treatment of advanced ovarian cancer.Method:Fifty-four patients with advanced ovarian cancer in our hospital were randomly selected from the beginning of July 2018 to the end of June 2019.The principle of grouping was based on double-blind randomization method.In experimental group,27 patients were given intraperitoneal administration of paclitaxel combined with cisplatin.In control group,27 patients were given intravenous administration of paclitaxel combined with cisplatin.Clinical data of the two groups were compared.Results:Short-term clinical efficacy and T lymphocyte subsets of experimental group were significantly improved when compared with control group.The difference was significant(P<0.05).There was no significant difference in adverse reactions between the two groups(P>0.05).Conclusion:The effect of intraperitoneal administration of paclitaxel combined with cisplatin is ideal for treatment of advanced ovarian cancer patients.
文摘AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.