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      A systematic review of gemcitabine and taxanes combination therapy randomized trials for metastatic breast cancer

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          Abstract

          Purpose

          Gemcitabine/taxanes-based combination shows anti-tumor activity for the treatment of metastatic breast cancer, but there is a debate regarding the advantages of gemcitabine and taxanes regimens as a first-line or second-line treatment for metastatic breast cancer. Here we conducted a systematic review and meta-analysis to compare the efficacy and toxicity for patients receiving chemotherapy with or without GT-based regimens.

          Methods

          The randomized controlled trials were performed by searching Pubmed, MEDLINE, EMBASE, and conference proceedings. We identified eight randomized controlled trials and then extracted and combined the data using to calculate hazard ratios (HR). The primary outcomes were progression-free survival (PFS) and time to progression (TTP). The secondary outcomes were overall survival (OS) and acute toxicity. A meta-analysis was performed using Review Manager Version 4.2.

          Results

          Eight eligible trails were identified. These studies involved 2234 patients with metastatic breast cancer, (1122 patients received GT-based combination regimen and 1112 patients received a regimen without the combination). A fixed-effects model meta-analysis showed that ORR and TTP are superior for GT-treated patients ORR (OR = 1.28, 95% CI 1.07-1.53), TTP (HR = 0.80; 95% CI 0.71-0.89). And GT-based combination significantly improved OS in the first-line subgroup (HR = 0.84; 95% CI 0.71-0.99). However, there were significant differences regarding acute hematological toxicity, particularly thrombocytopenia.

          Conclusion

          Gemcitabine/taxanes-treated patients with metastatic breast cancer showed a significant improvement in the ORR, TTP and OS (first-line background) compared to patients not treated with the combination regimen.

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          Most cited references28

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          Cancer Statistics, 2008

          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,437,180 new cancer cases and 565,650 deaths from cancer are projected to occur in the United States in 2008. Notable trends in cancer incidence and mortality include stabilization of incidence rates for all cancer sites combined in men from 1995 through 2004 and in women from 1999 through 2004 and a continued decrease in the cancer death rate since 1990 in men and since 1991 in women. Overall cancer death rates in 2004 compared with 1990 in men and 1991 in women decreased by 18.4% and 10.5%, respectively, resulting in the avoidance of over a half million deaths from cancer during this time interval. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. Although much progress has been made in reducing mortality rates, stabilizing incidence rates, and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
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            The global breast cancer burden: variations in epidemiology and survival.

            Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. However, the burden is not evenly distributed, and, according to the best available data, there are large variations in the incidence, mortality, and survival between different countries and regions and within specific regions. Many complex factors underlie these variations, including population structure (eg, age, race, and ethnicity), lifestyle, environment, socioeconomic status, risk factor prevalence, mammography use, disease stage at diagnosis, and access to high-quality care. We review recent breast cancer incidence and mortality statistics and explore why these vary so greatly across the world. Further research is needed to fully understand the reasons for variations in breast cancer outcomes. This will aid the development of tailored strategies to improve outcomes in general as well as the standard of care for underserved populations and reduce the burden of breast cancer worldwide.
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              Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial.

              Few chemotherapy agents are active in leiomyosarcoma (LMS), particularly LMS that has progressed after doxorubicin treatment. We sought to determine the response to gemcitabine plus docetaxel among patients with LMS. Patients with unresectable LMS of uterine (n = 29) or other (n = 5) primary sites who did not respond to zero to two prior chemotherapy regimens were enrolled onto a phase II study of gemcitabine 900 mg/m(2) intravenously (i.v.) on days 1 and 8 plus docetaxel 100 mg/m(2) i.v. on day 8 with granulocyte colony-stimulating factor given subcutaneously on days 9 to 15, delivered every 21 days. Patients with prior pelvic radiation received 25% lower doses of both agents. Gemcitabine was delivered over 30 or 90 minutes in cycles 1 and 2 and by 90-minute infusion in all subsequent cycles. Pharmacokinetic studies assessed in vivo differences in gemcitabine concentrations with different rates of infusion. Thirty-four patients (median age, 55 years; range, 32 to 74 years) have enrolled. Fourteen had received prior pelvic radiation. Sixteen of 34 patients had progressed after doxorubicin-based therapy; 18 had no prior chemotherapy. Among 34 patients, complete response was observed in three patients and partial response in 15, for an overall response rate of 53% (95% confidence interval, 35% to 70%). Seven patients had stable disease. Fifty percent of patients previously treated with doxorubicin responded. Hematologic toxicity was common (neutropenia: grade 3, 15%; grade 4, 6%; thrombocytopenia: grade 3, 26%; grade 4, 3%), but neutropenic fever (6%) and bleeding events (0%) were rare. The median time to progression was 5.6 months (range, 4 to 10 months). Gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with LMS.
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                Author and article information

                Contributors
                diana1007@126.com
                4941176@qq.com
                Luolongsysu@126.com
                yangx_325@qq.com
                linxiao0301@163.com
                416077413@qq.com
                zhwei36@mail2.sysu.edu.cn
                wujunyansysu@126.com
                yaoherui@163.com
                Journal
                Springerplus
                Springerplus
                SpringerPlus
                Springer International Publishing (Cham )
                2193-1801
                11 June 2014
                11 June 2014
                2014
                : 3
                : 293
                Affiliations
                [ ]Department of Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107 West Yangjiang Road, Guangzhou, 510120 PR China
                [ ]Department of Oncology, Yiyang Central Hospital of Hunan Province, No.232 West Wuyi Road, Yiyang, 413000 Hunan Province PR China
                [ ]Department of Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yangjiang Road, Guangzhou, 510120 PR China
                [ ]Pharmaceutical department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yangjiang Road, Guangzhou, 510120 PR China
                Article
                1550
                10.1186/2193-1801-3-293
                4447724
                7f97269c-03df-42af-968c-8a4fdf2ec36c
                © Hu et al.; licensee Springer. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 17 May 2014
                : 26 May 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Uncategorized
                metastatic breast cancer,gemcitabine,taxanes,systematic review
                Uncategorized
                metastatic breast cancer, gemcitabine, taxanes, systematic review

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