• Title, Summary, Keyword: gemcitabine

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Gemcitabine for the Treatment of Patients with Osteosarcoma

  • Wei, Mei-Yang;Zhuang, Yan-Feng;Wang, Wan-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7159-7162
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    • 2014
  • Background: Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with recurrent or refractory osteosarcoma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma.

An Updated Meta-analysis and System Review:is Gemcitabine+Fluoropyrimidine in Combination a Better Therapy Versus Gemcitabine Alone for Advanced and Unresectable Pancreatic Cancer?

  • Tu, Chao;Zheng, Feng;Wang, Jin-Yu;Li, Yuan-Yuan;Qian, Ke-Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5681-5686
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    • 2015
  • Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstline chemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited. The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients) (HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we found that in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12); while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95). Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

Mechanism of gemcitabine-induced apoptosis (Gemcitabine의 세포사멸 기전 연구)

  • Seol, Jae-Won;Lee, You-Jin;Kang, Dong-Won;Kang, Hyung-Sub;Kim, Nam-Soo;Kim, In-Shik;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.45 no.4
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    • pp.495-500
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    • 2005
  • The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours. Gemcitabine alone induced 35.3% cell death, and co-treatment with gemcitabine and Z-VAD-fmk induced 15.1% apoptotic cell death. Our results demonstrated that Z-VAD-fmk as a pan-caspase did not completely block the gemcitabine-induced apoptosis. Western blotting analysis showed that gemcitabine increased caspase-3, active caspase-8, p21 and p53 protein expressions in A549. Co-treatment with Z-VAD-fmk completely blocked caspase-3 and active caspase-8 protein expressions, but did not change the level of p21 and p53 protein expressions. Our data indicate that gemcitabine induced apoptosis through caspase-dependent and -independent pathways in A549.

Gemcitabine in Treating Patients with Refractory or Relapsed Multiple Myeloma

  • Zheng, Hua;Yang, Fan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9291-9293
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    • 2014
  • Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve the outcome. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In gemcitabine based regimens, 3 clinical studies which including 57 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 15.7% (9/57) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia i. No treatment related death occurred with gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with refractory or relapsed multiple myeloma.

Preparation of Gemcitabine-Loaded PLLA/Gemcitabine-PLLA Microparticles Using Supercritical Fluid and Their Release Characteristics (초임계 유체를 이용한 젬시타빈 함유 PLLA/젬시타빈-PLLA 미립자의 제조 및 방출 특성)

  • Hong, Jin-Hee;Lim, Giobin;Ryu, Jong-Hoon
    • KSBB Journal
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    • v.29 no.6
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    • pp.405-413
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    • 2014
  • In this study, gemcitabine (Gem)-Poly(L-lactic acid) (PLLA) conjugates were synthesized through an amide linkage reaction. Then, the microparticles of Gem-PLLA/PLLA blends containing gemcitabine were prepared using a supercritical fluid process, called aerosol solvent extraction system (ASES). Gemcitabine-loaded Gem-PLLA/PLLA microparticles obtained from the ASES process showed a spherical shape. The amount of gemcitabine released after 30 day incubation in a phosphate buffer solution of pH 7.4 was about 90% of the total amount of gemcitabine present in the product.

Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

  • Chanpanitkitchot, Saranya;Tangjitgamol, Siriwan;Khunnarong, Jakkapan;Thavaramara, Thaowalai;Pataradool, Kamol;Srijaipracharoen, Sunamchok
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5215-5221
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    • 2014
  • Background: To study the response rate (RR), progression-free survival (PFS) and toxicity profiles of recurrent epithelial ovarian cancer (EOC) patients treated with gemcitabine. Materials and Methods: Recurrent EOC patients who were treated with gemcitabine between January 2000 and December 2013 at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital were identified and medical records were reviewed. Clinico-pathological features including data of gemcitabine treatment, response and toxicity were collected. Results: We identified 43 EOC patients who had gemcitabine treatment. All except one patient who did not receive any adjuvant treatment, had received platinum-based chemotherapy. Among these 42 patients, 31.0% had refractory cancer to first-line chemotherapy while 69.0% had recurrence with 48.8% being platinum-sensitive. The total cycles of gemcitabine used were 203 (median 4, range 2-9 cycles). Overall RR was 11.6%: 19% in platinum-sensitive vs 4.5% in platinum-resistant groups (p=0.158) and 42.9% in the patients having gemcitabine together with platinum vs 5.6% using gemcitabine alone (P=0.024). Median PFS was 3.6 months (95% confidence interval [CI], 2.73-4.49 months): 8.1 months (95% CI, 2.73-4.49 months) in combination regimen vs 3.2 months (95% CI, 2.01-4.42 months) in single regimen (p=0.077) and 8.1 months (95% CI, 4.73-11.48 months) with the gemcitabine combination vs 2.7 months (95% CI, 1.98-3.38 months) by single gemcitabine in platinum sensitive patients (P=0.007). Common toxicities were hematologic which were well tolerated and manageable. Conclusions: Gemcitabine has modest activity in pre-treated EOC. A combination regimen had higher activity than single agent in platinum sensitive patients with a significant improvement in RR and PFS.

Gemcitabine Alone or in Combination with Cisplatin for Advanced Biliary Tract Carcinomas: an Overview of Clinical Evidence

  • Sun, Tian-Tian;Wang, Ji-Lin;Fang, Jing-Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.877-883
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    • 2013
  • Background and Objective: There has been no universally agreed standard chemotherapy regimen for patients with advanced biliary tract carcinomas (BTC). We aimed to fully display and evaluate the clinical evidence for gemcitabine or gemcitabine-cisplatin combination for advanced BTC. Methods: Systematic searches were performed to identify relevant randomized controlled trials (RCTs) and uncontrolled trials. Overall survival (OS), progression-free survival (PFS), overall response rates (ORR), tumor control rates (TCR), and toxicity were evaluated. Evidence levels of the results were evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Results of the eleven gemcitabine-cisplatin trials and ten gemcitabine trials showed both chemotherapy regimens had benefits with reference to mean OS (8.63 vs. 8.79 months), mean PFS (4.86 vs. 4.72 months), pooled ORR (25.3% vs. 19.6%) and TCR (55.2% vs. 53.1%). Two RCTs showed the gemcitabine-cisplatin combination to prolong the mean PFS (mean difference [MD] 2.57, 95%CI 1.69 3.45), substantially increasing the mean OS (MD 3.59, 95% CI 3.48 3.71), and producing a similar effect in ORR (risk ratio [RR] 1.59, 95%CI 1.04 2.43), increasing TCR (RR 1.15, 95%CI 1.02 1.31) compared with gemcitabine alone, with generally manageable grade 3 or 4 adverse events. The evidence level of OS was moderate, and other outcomes (ORR, PFS, TCR, anaemia, neutropenia) were at low evidence levels. Conclusion: Available evidence was limited with low quality, which showed that both gemcitabine-cisplatin and gemcitabine alone had clinical activity with acceptable safety profiles, and gemcitabine-cisplatin appeared to be more useful for advanced BTC patients than gemcitabine alone.

Anti-mutagenic Activity of Salvia merjamie Extract Against Gemcitabine

  • Alanazi, Khalid Mashay
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1501-1506
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    • 2015
  • Gemcitabine is an anti-cancer drug with clinically uses in the treatment of various neoplasms, including breast, ovarian, non-small cell lung, pancreaticand cervical cancers, T-cell malignancies, germ cell tumours, and hepatocellular carcinomas. However, it has also been reported to have many adverse effects. Naturally occurring anti-mutagenic effects, especially those of plant origin, have recently become a subject of intensive research. The present study was therefore designed to investigate the anti-mutagenic effects of Salvia merjamie (Family: Lamiaceae) plant extracts against the mutagenic effects of gemcitabine. The anti-mutagenic properties of Salvia merjamie were tested in Inbred SWR/J male and female mice bone marrow cells. The mice were treated in four groups; a control group treated with 30 mg/kg body weight gemcitabine and three treatment groups, each with 30 mg/kg body weight gemcitabine together with, respectively, 50, 100 and 150 mg/kg body weight Salvia merjamie extract. Chromosomal aberration and mitotic index assays were performed with the results demonstrating that Salvia merjamie extract protects bone marrow cells in mice against gemcitabine induced mutagenicity. This information can be used for the development of a potential therapeutic anti-mutagenic agents.

A Pooled Study on Combination of Gemcitabine and Nedaplatin for Treating Patients with Non-small Cell Lung Cancer

  • Yang, Song
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5963-5966
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    • 2015
  • Background: This analysis was conducted to evaluate the efficacy and safety of a combination of gemcitabine and nedaplatin in treating patients with non-small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of a combination of gemcitabine and nedaplatin with attention to response and safety for patients with non-small cell lung cancer were identified using a predefined search strategy. Pooled response rates for gemcitabine and nedaplatin were calculated. Results: In gemcitabine and nedaplatin based regimens, 4 clinical studies including 112 patients with non-small cell lung cancer were considered eligible for inclusion. The pooled analysis suggested that the pooled reponse rate was 40.2% (45/112). Main side effects included grade 3-4 neutropenia, thrombocytopenia, and anemia. Grade 3-4 nonhematological toxicity included nausea and vomiting, diarrhea, and hepatic dysfunction. There were no treatment-related deaths. Conclusion: This evidence based analysis suggests that the combination of gemcitabine and nedaplatin is associated with good response rate and accepted toxicity for treating patients with non-small cell lung cancer.

Comparison of Single Agent Gemcitabine and Docetaxel in Second-Line Therapy for Advanced Stage Non-Small Cell Lung Cancer in a University Hospital in Turkey

  • Yildirim, Fatma;Baha, Ayse;Yurdakul, Ahmet Selim;Ozturk, Can
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7859-7863
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    • 2015
  • Purpose: To compare the efficacy and toxicity of gemcitabine versus docetaxel in a second-line setting of nonsmall cell lung cancer (NSCLC) patients previously treated with platin-based combination chemotherapy. Materials and Methods: We retrospectively evaluated the medical records of 57 patients treated with single agent gemcitabine or docetaxel in second-line setting of advanced NSCLC who received one prior platinum-based therapy. Results: The mean age was $56.7{\pm}8.39$ years with 55 (96.5%) males and two (3.5%) females. Forty of them received docetaxel and 17 gemcitabine. The mean number of chemotherapy cycles was $6.8{\pm}4.0$ in the gemcitabine group, while it was $4.6{\pm}3.0$ in the docetaxel group. Overall response rates were 8% and 12% (P=0.02) for gemcitabine and docetaxel, respectively. The median survival time was 22 versus 21 months for gemcitabine and docetaxel, respectively. The median times to progression were 8 and 5 months. There was no difference between the two groups in terms of incidence of adverse affects (40% vs 47.1%). All of the hematological side effects were grade 1/2. No major toxicity was encountered necessitating stopping the drug for either group. Conclusions: Treatment with gemcitabine demonstrated clinically equivalent efficacy with a significantly improved safety profile compared with those receiving docetaxel in the second-line setting for advanced NSCLC in this study. Based on these results, treatment with gemcitabine should be considered a standard treatment option for second-line NSCLC.