Objective To introduce the research progress in the effect of chemotherapeutic resistance of metabolic enzymes of gemcitabine to pancreatic cancer.Methods Recent literatures about metabolic enzymes that played key roles in mediating gemcitabine chemotherapeutic resistance of pancreatic cancer were collected and reviewed. Results The metabolic enzymes of gemcitabine, such as hENT1, dCK, RRM1 and CDA, were closely related to chemotherapeutic resistance of pancreatic cancer. The relationship between the single nucleotide polymorphism of metabolic enzymes and the resistance to gemcitabine remained to be clarified. Conclusion Multiple factors are involved in the mechanism of chemotherapeutic resistance of pancreatic cancer to gemcitabine, which needs further research.
【Abstract】Objective To investigate the possible mechanism of gemcitabine resistance in pancreatic cancer chemotherapy. Methods Recent literatures about the genes and signal pathways those play key roles in mediating gemcitabine chemotherapy resistance of pancreatic cancer were collected and reviewed.Results Oncogenes like c-Src and bcl-XL, inflammation pathway of NF-κB, cytokines like IL-1β and NO are closely related with the chemoresistance； the relationship between multiple drug resistance relevant genes like MDR1/P-gP and the resistance to gemcitabine remains to be clarified. Conclusion Genes and pathways like c-Src, bcl-XL, NF-κB, etc. might become new targets to increase the chemotherapeutic sensitivity of pancreatic cancer, however, the mechanism of pancreatic cancer chemotherapy resistance still needs further to be studied.
ObjectiveTo evaluate the efficacy and toxicity of gemcitabine, paclitaxel plus cisplatin (GTP) chemotherapy for advanced urothelial carcinoma in China. MethodsTen patients with advanced urothelial carcinoma who underwent GTP chemotherapy regimens were collected from February to July 2014 in our hospital. According to solid tumor curative effect evaluation standard 1.1, we evaluated the clinical effcacy and collected the adverse reactions. ResultsTen patients with advanced urothelial carcinoma accepted first-line chemotherapy using GTP chemotherapy regimens. There was 1 case of complete remission, 4 cases of partial response, 3 stable cases, and 2 progressive cases. Adverse reactions of degree Ⅲ were mainly of hematology toxicity, including 5 cases of leukocytes and neutrophils reduction, and 1 case of anemia. The remaining adverse reactions included gastrointestinal reaction, hair loss, and abnormal renal function. ConclusionGTP chemotherapy regimen is a promising treatment for advanced urothelial carcinoma.
ObjectiveTo observe the alteration of serum homocysteine (Hcy) levels of advanced non-small cell lung cancer (NSCLC) patients during gemcitabine with cis-platinum (GP) program of chemotherapy and to explore the clinical value of monitoring Hcy in evaluating chemotherapy curative effect. MethodsA total of 49 advanced NSCLC patients (including 28 squamous carcinoma and 21 adenocarcinoma) first treated between May 2012 and April 2015 were selected. The Hcy, cytokerantin-19-fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) levels of the morning fasting venous blood were measured before the first and after the second cycle of chemotherapy. Combined the pathological types of NSCLC, statistical analysis was carried out on the test results. ResultsAll of the 49 patients completed two cycles of GP chemotherapy, and the chemotherapy was effective on 31 and ineffective in 18. Before the chemotherapy, the differences in the positive rates of Hcy, CYFRA21-1, and CEA were statistically significant respectively between squamous carcinoma and adenocarcinoma patients (P < 0.05). But when combined the two types, the differences of three indicators's positive rates were not significant (P > 0.05). After two cycles of GP chemotherapy, in the patients with effective chemotherapy, the Hcy, CYFRA21-1 and CEA levels were lower in both squamous carcinoma and adenocarcinoma patients compared with that before the chemotherapy; the difference in the decrease of Hcy levels in both of the two pathological types was significant (P < 0.05), while CEA levels was significant only in adenocarcinoma patients (P < 0.05) and CYFRA21-1 levels was significant only in squamous carcinoma patients (P < 0.05). Among the patients with ineffective chemotherapy, the Hcy, CYFRA21-1 and CEA levels increased compared with those before the chemotherapy; the difference in the increase of Hcy levels were significant in both of the two pathological types (P < 0.05), while CYFRA21-1 levels was significant only in squamous carcinoma patients (P < 0.05) and CEA levels was not significant in both of the two pathological types (P > 0.05). ConclusionThe effect of chemotherapy and the pathogenetic condition can be assessed by monitoring serum Hcy levels of NSCLC patients during the chemotherapy.
ObjectiveTo systematically review the effectiveness and safety of Kanglaite combined with gemcitabine in treating patients with advanced non-small cell lung cancer (NSCLC). MethodsThe randomized controlled trials (RCTs) about Kanglaite ombined with gemcitabine treating advanced NSCLC was retrieved in PubMed, EMbase, The Cochrane Library (Issue 9, 2013), CBM, CNKI, VIP, and WanFang Data from the dates of their establishment to September 2013. Literature screening according to the inclusion and exclusion criteria, data extraction and methodological quality assessment were completed by two reviewers independently. Meta-analysis was then conducted using RevMan 5.2 software. ResultsA total of seven RCTs involving 506 patients were finally included. The results of meta-analysis indicated that:a) Kanglaite injection combined with gemcitabine chemotherapy increased short-term effectiveness (OR=1.85, 95%CI 1.29 to 2.65, P=0.000 8), patients' quality of life (OR=3.02, 95%CI 1.90 to 4.78, P < 0.000 1), and immune function (MD=0.64, 95%CI 0.31 to 0.97, P=0.000 1); and reduced the incidences of leukopenia decrease (OR=0.30, 95%CI 0.19 to 0.47, P < 0.000 01), nausea and vomiting (OR=0.49, 95%CI 0.34 to 0.73, P=0.000 3), bone marrow suppression (OR=0.27, 95%CI 0.16 to 0.45, P < 0.000 01), and liver and renal impairments (OR=0.43, 95%CI 0.28 to 0.68, P=0.000 3), all with significant differences. b) Both groups were alike in reducing thrombocytopenia (OR=0.67, 95%CI 0.40 to 1.14, P=0.14) without significant differences. ConclusionApplying Kanglaite injection combined with gemcitabine in treating patients with advanced NSCLC could increase short-term effectiveness, improve patients' quality of life and immune function; and reduce the incidences of adverse reaction caused by chemotherapy. However, it has no obvious advantage in reducing thrombocytopenia. Due to the limited quantity and quality of the included studies, more larger sample size, multicenter, high quality RCT are needed to verify the above conclusion.
ObjectiveTo expolre the effect and safety of gemcitabine combined with docetaxel in the treatment of advanced breast cancer. MethodsForty-eight breast cancer patients who got treatment by gemcitabine combined with docetaxel from March 2013 to March 2014 were prospectively enrolled in this study. ResultsOf all the 48 patients, the completely responded (CR) rate was 16.7%(8/48), partial responded (PR) rate was 35.4%(17/48), stable disease (SD) rate was 33.3% (16/48), progressive disease (PD) rate was 14.6% (7/48), and the response rate was 52.1% (25/48), the clinical benefit rate was 85.4% (41/48). The response rates of hormone receptor (HR)-positive group, human epidermal growth factor receptor 2 (HER-2)-positive group, and Basal-like group were 43.5% (10/23), 54.5% (6/11), and 64.3% (9/14) respectively, the clinical benefit rates of HR-positive group, HER-2-positive group, and Basal-like group were 82.6% (19/23), 81.8% (9/11), and 92.9% (13/14) respectively. There was no significant difference among the 3 groups in the effect, response rate, and clinical benefit rate (P=0.293, P=0.462, P=0.663). All patients suffered from varying degrees of toxicities during chemotherapy, including leukopenia, neutropenia, decreased hemoglobin, thrombocytopenia, rash, nausea, vomiting, hair loss, diarrhea, fatigue, and elevated alanine aminotransferase, wherein leukopenia (27.1%, 13/48), neutropenia (22.9%, 11/48), thrombocytopenia (4.2%, 2/48), and fatigue (10.4%, 5/48) were included inⅢ-Ⅳ degree of adverse reactions. In addition, all of 48 patients were followed-up for 1-19 months, with a median follow-up time of 12 months. During follow-up period, 6 patients died, and the overall survival rate was 87.5% (42/48). There was no significant difference among the 3 groups in overall survival and progression free survival (P > 0.050). ConclusionGemcitabine combined with docetaxel may be an effective therapy in treatment of advanced breast cancer.
Objective To observe the early efficacy and toxicity of gemcitabine plus tegafur, gimeracil and oteracil potassium (S-1) regimen (GS regimen) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. Methods From July 2013 to December 2015, sixteen mCRPC patients who failed in the treatment of docetaxel-based chemotherapy in West China Hospital of Sichuan University were collected. And the patients were treated with gemcitabine 1 000 mg/m2 intravenously on Day 1 and S-1 40–60 mg/m2 orally dividedly twice daily on Day 1–10, which repeated every two weeks. The main outcome measures were total prostate-specific antigen (T-PSA) decline rate and pain remission rate. Results Of the 13 evaluable patients, the T-PSA decline rate≥50% was observed in 4 patients (30.8%). Among the 11 patients with bone pain, remarkable pain relief was observed in 4 cases (36.4%). Myelosuppression, gastrointestinal reaction, rash and fatigue were the commonly observed adverse reactions and the toxicity of chemotherapy was tolerable. Conclusion The GS regimen is active and tolerable in patients with mCRPC after docetaxel failure.
Objective To evaluate the efficacy and safety of capecitabine combination chemotherapy for advanced pancreatic cancer. Methods The Cochrane Library, PubMed, EMbase, CBM, CNKI and WanFang Data databases were searched to collect randomized controlled trials (RCTs) on capecitabine combination chemotherapy for advanced pancreatic cancer from inception to December, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, data were analyzed by using RevMan 5.3 software. Results Six RCTs were included. The results of meta-analysis showed that compared with the control group, capecitabine combination chemotherapy extended the overall survival (HR=0.86, 95%CI 0.77 to 0.96, P=0.006) and disease progression-free survival (HR=0.83, 95%CI 0.75 to 0.91, P=0.000 2). Moreover, the objective response rate was significantly increased in capecitabine combination chemotherapy (RR=1.64, 95%CI 1.27 to 2.11, P=0.000 1). The results of 3–4 toxic side effects of 6 RCTs indicated that the incidence of neutropenia, stomatitis and hand-foot syndrome of capecitabine combination chemotherapy were obviously higher than those in the control group (P<0.05). Conclusions Capecitabine combination chemotherapy extend the overall survival and disease progression-free survival, and improve the objective response rate. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
ObjectivesTo evaluate the economic efficacy of nab-paclitaxel (NAB-P) combined with gemcitabine (GEM) versus GEM alone in the treatment of metastatic pancreatic cancer in China.MethodsA Markov model simulating the costs and health outcomes was developed to estimate quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). The impact of parameter uncertainty on the model was assessed by deterministic one-way sensitivity analysis.ResultsNAB-P combined with GEM was shown superior efficacy compared to gemcitabine monotherapy, however with higher costs. The ICER between the two groups was 964 780.79￥/QALY.ConclusionsCompared with gemcitabine monotherapy, NAB-P combined with GEM is not cost-effective. The conclusion is confirmed by deterministic one-way sensitivity analysis.