Objective To assess the clinical effectiveness and safety of paclitaxel liposomes and carboplatin for ovarian cancer. Methods The databases such as The Cochrane Library, PubMed, EMBASE, CNKI and CBM were searched to collect all randomized control trials (RCTs) about the clinical effectiveness and safety of paclitaxel liposomes and carboplatin for ovarian cancer. Literatures were screened according to the inclusive and exclusive criteria, the data were extracted, the methodological quality of the included studies was assessed in line with Cochrane Handbook 5.0.1, and Meta-analysis was performed by using RevMan 5.0.24 software. Results Three RCTs involving 214 patients were included. Meta-analysis showed that compared with the paclitaxel plus carboplatin group, the paclitaxel liposomes plus carboplatin group didn’t show significant differences in the total effective rate (P=0.62), while it was obviously superior in reducing the adverse events, such as muscle and joint pain (Plt;0.000 01), peripheral neurotoxicity (P=0.04), nausea or vomiting (P=0.000 2), facial blushing (P=0.03) and rashes (P=0.003). But there were no significant differences between the two groups in trichomadesis, dyspnea, diarrhea, bellyache and blood system abnormalities. Conclusion As current clinical evidences shows, the paclitaxel liposomes and carboplatin in treating ovarian cancer is as effective as the paclitaxel and carboplatin, and it can reduce some of the adverse reactions. Therefore, the paclitaxel liposomes and carboplatin is available for ovarian cancer as a new, safe and effective treatment. Due to small scale and low quality of the included studies, this conclusion has to be further proved with more high-quality, large-scale, and double-blind RCTs.
Abstract: Objective To investigate the effect of keeping implanted vein graft from restenosis by local application of paclitaxel. Methods Ninetysix New Zealand rabbits were randomly divided into three groups, control group (n=32), group Ⅰ(n=32), group Ⅱ(n=32). The vein graft stenosis model was made in all rabbits. In group Ⅰand group Ⅱ, 1μg and 8μg of paclitaxel was applied locally in pluronic gelatin respectively. There were no local treatment in control group. Grafts were harvested at 1, 2, 4, and 6 weeks and underwent morphological analysis as well as immunohistochemical analysis. Results The intimal thickness in group Ⅱ were significantly decreased compared to those in control group at 1,2,4, and 6 weeks after operation (30.10±4.50μm vs. 48.20±9.16μm, 40.70±6.91μm vs. 54.20±8.67μm, 54.70±7.11μm vs. 68.60±13.72μm, and 68.70±8.24μm vs. 76.40±12.98μm, Plt;0.05). The CD8 positive cells and metallothionein positive cells in group Ⅰand group Ⅱ were significantly decreased compared to those in control group (Plt;0.05). Conclusion The results suggest that perivascular application of paclitaxel inhibits neointimal hyperplasia of vein grafts in a rabbit model, and paclitaxel may have a therapeutic potential for the treatment of vein graft disease.
Abstract:Objective To investigate immunoinh.ibitory effects of paclitaxel on acute rejection of allogeneic heart transplantation in rats. Methods Heterotopic abdominal cardiac transplantation was performed from Wistar rats to SD rats. Seventy recipients were randomly divided into five groups,14 rats in each group. Control group： rats didn＇t receive any immunoinhibitory drug; group Ⅰ ： low-dose paclitaxel （0.75 mg/kg · d） was injected intraperitoneally; group Ⅱ ： high-dose paclitaxel （1.5 mg/kg ·d） was injected intraperitoneally; group Ⅲ ： cyclosporin A（CsA, 5 mg/ kg·d） was administered orally; group Ⅳ ： low-dose paclitaxel （0. 75 mg/kg · d） was injected intraperitoneally in combination with CsA （5 mg/kg · d administered orally）. General conditions of recipient, allograft survival and pathologic lesion at 7th day posttransplantation were observed. Results Allograft survival in treating groups were significantly prolonged compared with control group （P〈 0. 05）. Moreover, allograft survival in group IV was significantly prolonged compared with those in group Ⅰ and group Ⅲ （P〈0.05）. On 7th day posttransplantation, cardiac allograft looked swollen and International Society for Heart and Lung Transplantation （ISHLT） score was 3 or 4 in control group; cardiac allograft beat vigorously, showed pink in color and felt tender in group Ⅰ and group Ⅱ , ISHLT-score was 2 or 3. Compared to control group, pathologic lesion of grafts in group Ⅰ and group Ⅱ were significantly relieved （P〈0.05）. Cardiac allograft beat well and ISHLT-score was 2 in group Ⅲ. Cardiac allograft looked as normal and beat vigorously, ISHLT-score was less than 2 in group IV ; the protective effects on cardiac allograft was better than those in group Ⅰ and group Ⅱ （P〈0. 05）. Conclusion Paclitaxel could obviously suppress acute rejection and prolong survival of rat cardiac allograft. Paclitaxel and CsA has synergistic effect on prevention acute rejection.
Objective To determine the effectiveness and safety of weekly versus three weekly regimens of taxanes for non-small cell lung cancer (NSCLC). Methods We searched The Cochrane Library (Issue 1, 2008), PubMed (1966 to May 2008), EMbase (1974 to May 2008), and CBM (1978 to May 2008) to identify randomized controlled trials (RCTs) which compared weekly and three weekly regimens of taxanes for NSCLC. Data collection was undertaken by two reviewers independently; the methodological quality was assessed according to the Cochrane Handbook 4.2.6; and the meta-analyses were performed using RevMan 5.0 software. Results Nine RCTs involving 1 438 patients were included. The results of meta-analyses showed: (1) There were no significant differences in the efficacy between weekly and three weekly regimens of taxanes regarding the one-year survival rate (paclitaxel: RR=1.24, 95%CI 0.83 to 1.86; docetaxel: RR=0.80, 95%CI 0.51 to 1.23) and the overall response rate (paclitaxel: RR=1.03, 95%CI 0.72 to 1.49; docetaxel: RR=0.98 95%CI 0.64 to 1.49). (2) The incidence of neutropenia was less serious in the weekly group (paclitaxel: RR=0.74, 95%CI 0.56 to 0.97; docetaxel: RR=0.22, 95%CI 0.16 to 0.30), while no significant differences existed in other adverse effects such as anemia and nausea/vomiting. Conclusion The efficacy of weekly and three weekly regimens of taxanes for the treatment of NSCLC is similar. The incidence of neutropenia is lower in the weekly group while other toxicities show no differences.
Objective To assess the clinical efficacy and safety of paclitaxel in the first-line and second-line treatment of patients with small cell lung cancer (SCLC). Methods We searched The Cochrane Library, MEDLINE, EMBASE, CBM, CNKI, VIP and etc to collect all clinical controlled trials involving the addition of paclitaxel to chemotherapy in SCLC patients. Two reviewers evaluated the quality of included trials independently. The Cochrane Collaboration’s software RevMan 4.2.2 was used for meta-analyses. Results Nine trials involving 1675 SCLC patients were included. Five trials were randomized controlled trials, and all trails didn’t mention the blinding methods. Meta analyses indicated that the PET arm (paclitaxel+cisplatin+etoposide) had a similar response rate compared with the EP arm (etoposide+cisplatin) (OR1.35, 95%CI 0.98 to 1.85). The incidences of severe thrombocytopenia (OR 1.68, 95%CI 1.12 to 2.52) and lethal toxicity (OR 4.00, 95%CI 1.77 to 9.04) were higher in the PET arm than those in the EP arm, but the incidence of severe leukocytopenia was lower in the PET arm (OR 0.50, 95%CI 0.37 to 0.68). A total of 54 treatment-related deaths were reported. Conclusion In the first-line treatment of SCLC, the combination of paclitaxel, carboplatin and etoposide improved the progression-free survival, but the combination of paclitaxel and EP did not improve the survival and was more toxic than EP alone. Paclitaxel as the second-line treatment showed some therapeutic effect. Due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.
Objective To assess the clinical efficacy, safety and cost-effectiveness of topotecan for recurrent epithelial ovarian cancer. Methods We searched MEDLINE (1966 to 2005), EMbase (1989 to 2004), CancerLit (1996 to 2003), CBMdisc (1978 to 2005), CNKI (1994 to 2005), The Cochrane Library (Issue 3, 2005), The National Research Register, and the Health Technology Assessment Database (HTA). Relevant journals were also handsearched. The search was conducted on December 31, 2005. Randomize controlled trials (RCTs) comparing topotecan versus other agents for recurrent epithelial ovarian cancer were included. The quality of the eligible trials was assessed by two reviewers independently. Meta-analysis was performed. Results Four RCTs met the inclusion criteria, and the methodological quality was either level A or B. When used as second-line chemotherapy for recurrent ovarian cancer, there was no significant difference in remission rate between topotecan and paclitaxel or pegylated liposomal doxorubicin (PLD). The clinical benefit rate of topotecan was higher than that of paclitaxel or PLD. Myelosuppression was more frequent in patients in the topotecan group than those in the PLD or paclitaxel group, but it was not severe. As to cost-effectiveness analysis, topotecan was better than PLD. Conclusions The standard regimen of topotecan (intravenous 1.5 mg/m2/d for 5 consecutive days) is recommended for use in platinum-resistant and refractory ovarian cancer.
Objective To evaluate the effect of neoadjuvant chemotherapy on the expression of CXCR4 in breast cancer and its clinical significance.Methods The clinical data of 59 patients with breast cancer of stage Ⅱ and stage Ⅲ underwent neoadjuvant chemotherapy with paclitaxel plus epirubicin for 3 cycles between April 2005 and March 2009 were retrospectively analyzed. The expression of CXCR4 in the breast cancer tissues before and after neo-adjuvant chemotherapy was examined by immunohistochemistry and its relationship with clinicopathologic factors was analyzed.Results The CXCR4 positive expression was observed in 56 patients with breast cancer (94.9%), but not in corresponding nontumor normal tissues. The expression level of CXCR4 was correlated to lymph nodes metastasis (P=0.019) and breast cancer stage (P=0.040), but it was not correlated to age of patients, tumor size, grade, hormone receptor (ER and PR)， and HER2 status. The expression level of CXCR4 was significantly decreased after neoadjuvant chemotherapy. Decline extent of CXCR4 expression after chemotherapy and CXCR4 expression level were not correlated to the effect of neoadjuvant chemotherapy, while the effect of chemotherapy in patients expressed CXCR4 in cluster distribution was better than that in scattering distribution (P=0.015). Conclusion The decline extent of CXCR4 expression level after paclitaxel combined with epirubicin neoadjuvant chemotherapy is not correlated to the efficacy, but its expressing distribution may be considered as an index to the effect of neoadjuvant chemotherapy.
ObjectiveTo compare the recent efficiency and toxicity reactions of pemetrexed plus cisplatin and paclitaxel plus cisplatin for advanced lung adenocarcinoma. MethodsOne hundred and twenty-four patients with advanced lung adenocarcinoma treated in our hospital between January 2009 and December 2012 were divided into pemetrexed plus cisplatin group (group PP, n=63) and paclitaxel plus cisplatin group (group TP, n=61). The effect was evaluated after two courses of treatment, and the toxicity reactions were evaluated every course. ResultsThe objective response rate, disease control rate and progression-free survival in group PP and TP were respectively 58.7% vs 37.7%, 74.6% vs 52.5%, and 6.1 months vs 4.5 months, with significant differences (P<0.05). The incidence of nausea and vomiting, and white blood cell decrease (neutropenia) in group PP were significantly lower than that in group TP (χ2=16.164, P<0.001; χ2=9.469, P=0.002). There were no significant differences in incidence of thrombocytopenia, anemia and hepatic function damage (χ2=0.098, P=0.755; χ2=0.267, P=0.606; χ2=0.006, P=0.973). ConclusionPemetrexed plus cisplatin shows obviously superior effects and fewer side effects on advanced lung adenocarcinoma compared with paclitaxel plus cisplatin regime.
ObjectiveTo evaluate the therapeutic effect and adverse reaction of paclitaxel liposome combined with continuous infusion of large-dose 5-fluorouracil(5-fu) in treatment for advance gastric cancer(AGC). MethodsFrom May 2009 to August 2012, 63 consecutive patients with AGC in this hospital were enrolled in this study. All the patients were given chemotherapy including paclitaxel liposome and continuous infusion of large-dose(2.5 g/m2) 5-fu. The efficacy and toxicity of this regimen were observed. ResultsThere was no patient who could not tolerate adverse reaction related to such regimen. Five cases achieved complete response and 31 cases achieved partial response, the overall response rate was 57.1%(36/63). Hematologic toxicity included gradeⅢ/Ⅳleucopenia 8 cases(12.7%) and neutropenia 10 cases(15.9%), while there was no occurrence of gradeⅢ/Ⅳanemia or thrombopenia. Non-hematologic toxicity was fairly mild. ConclusionsPaclitaxel liposome is safe, well tolerated, highly targeted, and has long duration of effect. Paclitaxel liposome combined with continuous infusion of large-dose 5-fu is safe and effective in treatment for patients with AGC.
ObjectiveTo investigate the inhibitory effect of heat shock protein 90 (HSP90) inhibitors of 17-propylene amino-17-demethoxy geldanamycin (17-AAG) combining with paclitaxel on human anaplastic thyroid cancer FRO cell line. Method①The proliferation inhibition rates of FRO cells were detected by mmethyl thiazolyl tetrazolium (MTT) assay in different concentration groups (17-AAG: 0.312 5, 0.625 0, 1.2500, 2.5000, and 5.0000 μmol/L; paclitaxel: 0.001 0, 0.0100, 0.1000, and 1.0000 μmol/L; combination group, 17-AAG: 0.625 0 μmol/L, paclitaxel: 0.001 0, 0.0100, 0.1000, and 1.0000 μmol/L) and at different time points (24, 48, and 72 hours). ②The change of cell cycle and apoptosis rates of FRO cells were detected in 17-AAG group (0.625 0 μmol/L), paclitaxel group (0.1000 μmol/L), and combination group (17-AAG: 0.625 0 μmol/L, paclitaxel: 0.1000 μmol/L) by flow cytometry at 24 hours after treatment. ③activity of Caspase-3 and Caspase-9 in FRO cells of 17-AAG group (0.625 0 μmol/L), paclitaxel group (0.1000 μmol/L), and combination group (17-AAG: 0.625 0 μmol/L, paclitaxel: 0.1000 μmol/L) was detected by Caspase-3 detection reagent box and Caspase-9 detection reagent box respectively. FRO cells of normal control group were treated without any drug, but culture solution. Results①The proliferation inhibition rates of FRO cells increased with the increase of concentra-tion (17-AAG, paclitaxel, combination of 17-AAG and paclitaxel), there was significant difference between any 2 groups (normal control group included), P<0.05. In addition, the proliferation inhibition rates of FRO cells in any concentration group (normal control group excluded) increased over time (24, 48, and 72 hours), there was significant difference between any 2 time points (P<0.05). The proliferation inhibition rates of FRO cells in combination group were all higher than those of 17-AAG group and paclitaxel group in condition of same time point and same concentration (P<0.05). The q value of combination group was higher than 1.15 at 3 time points in all concentration, that meant 17-AAG could increase the efficiency of paclitaxel. ②The apoptosis rate of FRO cells in normal control group was lower than those of 17-AAG group, paclitaxel group, and combination group (P<0.05), and apoptosis rate of FRO cells in combination group was higher than those of 17-AAG group and paclitaxel group (P<0.05). ③Activity of Caspase-3 and Caspase-9 of FRO cells in normal control group were lower than those of 17-AAG group, paclitaxel group, and combination group (P<0.05), and activity of Caspase-3 and Caspase-9 of FRO cells in combination group were higher than those of 17-AAG group and paclitaxel group (P<0.05). Conclusions17-AAG and paclitaxel can significantly inhibit the proliferation and induce the apoptosis of FRO cells. The combination of the two kinds of drugs may generate synergy, with dose-dependence effect.