Evaluation Of Gemcitabine Research Articles

Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

PO-92 Evaluation of gemcitabine and platinum agents for the prediction of venous thromboembolism in patients with cancer: results from the Vienna Cancer and thrombosis Study

PO-92 Evaluation of gemcitabine and platinum agents for the prediction of venous thromboembolism in patients with cancer: results from the Vienna Cancer and thrombosis Study

Abstract 4650: Pharmacokinetic and pharmacodynamic study of adjuvant gemcitabine therapy of biliary tract cancer following major hepatectomy (KHBO1101)

Abstract Background: Gemcitabine at a standard dose of 1000 mg/m2 on Day 1, 8 and 15 every 4 weeks is not tolerated in biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy determined that the recommended dose is 1000 mg/m2 on Day 1 and 15 every 4 weeks. Here, we evaluated the pharmacokinetics and pharmacodynamics of gemcitabine at this recommended dose. Methods: This study evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by postoperative gemcitabine therapy. Pharmacokinetic evaluation of gemcitabine and 2′,2′-difluorodeoxyuridine (dFdU) was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800 to 1000 mg/m2. Physical examination and adverse events were assessed for two weeks. Results: Thirteen patients were enrolled from August 2011 to January 2013, with 12 completing the study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had distal extrahepatic cholangiocarcinoma. Median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43-83 days). In the twelve patients, the following disorders at all grades of severity were observed: leukopenia (83.3%), neutropenia (66.7%), and thrombocytopenia (50.0%). Further, Grade 3 of neutropenia was observed in 16.7% of these patients. The dose-normalized AUC of gemcitabine and dFdU in patients with major hepatectomy was 10.22 ± 2.54 and 94.38 ± 45.38 mg/L/hr, respectively. These values were generally similar to those of patients with pancreatic cancer who did not undergo hepatectomy in a previous study. Conclusion: This study demonstrated that major hepatectomy did not affect the pharmacokinetics of gemcitabine and dFdU, despite an increase in hematological toxicity. Citation Format: Yutaka Fujiwara, Shogo Kobayashi, Hiroaki Nagano, Masashi Kanai, Etsuo Hatano, Masanori Toyoda, Tetsuo Ajiki, Yuki Takashima, Akinobu Hamada, Hironobu Minami, Tatsuya Ioka. Pharmacokinetic and pharmacodynamic study of adjuvant gemcitabine therapy of biliary tract cancer following major hepatectomy (KHBO1101). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4650. doi:10.1158/1538-7445.AM2014-4650

Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia

Our aim was to estimate the duration of maximum tolerated dose (MTD) duration for gemcitabine given as a continuous infusion in combination with fludarabine and mitoxantrone and to evaluate potential pharmacokinetic (PK) interactions in 17 patients with refractory or relapsed acute myeloid leukaemia (AML). Gemcitabine was administered at 10 mg/m2/min for 3–15 h, fludarabine at 25 mg/m2 daily for days 1–5 and mitoxantrone at 10 mg/m2 daily on days 1–3. PK studies revealed that fludarabine clearance was not affected by gemcitabine but mean terminal half-life and volume of distribution of fludarabine were slightly increased. The duration of MTD for gemcitabine was 12 h. Our previous in vitro work has demonstrated the binary combination of gemcitabine + fludarabine is most synergistic at a molar ratio around 0.002. However, with MTD dosing this drug ratio is not optimal to produce synergy and future studies using ratiometric dosing are required to confirm these findings.

Evaluation of gemcitabine plus carboplatin in pretreated, metastatic breast cancer patients: Final analysis of a phase II trial

1074 Background: There is an increasing proportion of metastatic breast cancer patients (pts) who have been exposed to anthracyclines and taxanes either during perioperative treatment or during intial therapy of metastatic disease. The efficacy of gemcitabine plus cisplatin has been consistently demonstrated in several trials. This study evaluates the combination of gemcitabine plus carboplatin as a treatment option for intensively pretreated breast cancer pts. Methods: Metastatic breast cancer pts were treated with gemcitabine (1,000 mg/m2 iv on days 1 and 8) and carboplatin (AUC 4 iv on day 1) in a 3-week regimen. The trial was performed as a 2-stage phase II study according to the optimal design described by Simon (p0 = 0.1, p1 = 0.3, a = 0.05, β = 0.1) with overall remission rate (according to RECIST) as the primary objective. Results: 39 pts were recruited, median age was 60 years (29–77 yrs): median Karnofsky performance status was 90% (range, 70–100%), 77% of pts were ER- and/or PR-positive, and 28% of pts presented with Her-2 overexpression (IHC 3+ or FISH-positive). 87% of pts had visceral metastasis and 79.5% had =2 sites of metastasis. All patients had received prior chemotherapy and 92% of pts had received prior anthracyclines (87%) and/or taxanes (67%). Prior endocrine therapy had been applied to 77% of patients. Median follow-up time was 13.2 months (1–27 months) during which 207 treatment cycles were documented with a median number of 5 cycles per pt (range 1–12). A CR was observed in 1 pt, a PR in 11 pts for an overall remission rate of 31% (95%-CI: 17–48%). Stable disease was documented in 12 pts (31%) resulting in a disease control rate of 61.5%. Median time to remission was 2.6 months (1.3–5.1 months), median time to progression was 4.9 months (95%CI, 2.6–6.7 months), and overall survival was 13,2 months (95% CI, 8.7–16.7 months). Grade 3–4 leucopenia (NCI-CTC) was observed in 64%, neutropenia in 51%, thrombocytopenia in 49%, and anemia in 10% of pts. Conclusion: Gemcitabine plus carboplatin is an effective and well tolerated treatment option in intensively pretreated breast cancer pts. No significant financial relationships to disclose.

Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group

Purpose A multicenter study was conducted to evaluate the activity and toxicity of gemcitabine in patients with previously treated non-squamous cell carcinoma of the uterine cervix. Patients and methods Eligible patients were required to have measurable disease with a GOG performance status of 0–2 and adequate bone marrow, renal, and hepatic function. Histologic confirmation of the primary diagnosis was mandatory. Patients were required to have received one prior chemotherapy regimen for metastatic, persistent or recurrent disease. The initial dosage of gemcitabine was 800 mg/m 2 weekly times three with 1 week off until progressive disease or adverse side effects prohibited further therapy. Doses were escalated or reduced based on the disease toxicity experiences during the previous cycle. Results Twenty-two women were entered into the trial. Three patients did not complete follow-up assessment for tumor response leaving 19 evaluable patients for response. All 22 patients were evaluable for toxicity. A median of two cycles was administered to each patient (range: 1–8). The overall response rate (1 partial response) was 4.5% with 36.4% of patients having stable disease. The median progression-free interval was 2.1 months (range: 0.5–12.7) and the overall survival was 6.5 months (range: 0.6–21.9). One patient had a grade 4 gastrointestinal adverse event (rectovaginal fistula formation attributed to the underlying cancer and not the study agent) complicated by grade 4 metabolic derangement. There were no grade 4 hematologic toxicities or treatment-related deaths. Conclusions Gemcitabine as a single agent had minimal activity in previously treated patients with non-squamous cell carcinoma of the uterine cervix.

Gemcitabine in cervical cancer

Objective Recurrent and advanced cervical cancers are associated with high mortality and a lack of effective treatment options, especially for women who are poor candidates for surgery or radiation therapy. The broad clinical effectiveness and low toxicity of gemcitabine in other human malignancies suggest that it might be useful in treating cervical tumors. Methods Fifteen phase I/II clinical trials on the use of gemcitabine, both as a single agent and in combination with cisplatin, in patients with recurrent or advanced carcinoma of the cervix were reviewed. Data from studies in which gemcitabine was used in combination with radiotherapy for induction therapy and with cisplatin for neoadjuvant chemotherapy were also evaluated. Results Although single-agent gemcitabine was generally inferior to cisplatin, when used concurrently with cisplatin and/or radiation therapy, objective response rates were high and survival was prolonged. The drug also showed promise when used with cisplatin as neoadjuvant therapy. Conclusions Initial studies suggest that gemcitabine may be useful in the management of recurrent or advanced cervical cancer when used concurrently with cisplatin. Accordingly, a large phase III study will compare cisplatin/gemcitabine with the current standard, and further evaluation of gemcitabine appears to be warranted in conjunction with radiotherapy and in the neoadjuvant setting.

Economic evaluation of gemcitabine in the treatment of pancreatic cancer in the UK

This study evaluated the cost-effectiveness of gemcitabine as first-line treatment for pancreatic cancer in the UK. Outcomes data and costs based on utilisation data were analysed from a previously reported clinical trial. Outcome measures were average and incremental costs of survival gain, progression-free survival gain and clinical benefit response (a symptom-based measure) for gemcitabine compared with 5-fluorouracil (5-FU) via intravenous injection in the first-line setting. The incremental costs per life-year and per progression-free life-year were pounds sterling 12,206 and pounds sterling 19,888, respectively, for gemcitabine over 5-FU therapy. The incremental cost per clinical benefit responder for gemcitabine over 5-FU was pounds sterling 12,142. If 5-FU was administered by 24-h continuous infusion rather than being given once a week, treatment costs were estimated to be more expensive. The resulting incremental cost per life-year gained with gemcitabine falls to pounds sterling 8,831. Sensitivity analyses (including alterations based on statistical variance) demonstrated that the results were robust and relatively insensitive to variations in key parameters. Gemcitabine is thus a cost-effective therapy for patients with pancreatic cancer and cost per life-year compares favourably with other technologies funded by the National Health Service in the UK.

Evaluation of Gemcitabine in Patients with Squamous Cell Carcinoma of the Cervix: A Phase II Study of the Gynecologic Oncology Group

Purpose. A multicenter Phase II trial was conducted to evaluate the activity and toxicity of gemcitabine in patients with previously treated squamous cell carcinoma of the uterine cervix.Patients and methods. Patients were required to have measurable disease with adequate performance status, bone marrow, hepatic, and renal function. Histologic confirmation of the primary diagnosis as squamous cell cancer of the uterine cervix was mandatory. Patients were allowed one prior chemotherapy regimen, usually cisplatin-based. The initial dose of gemcitabine was 800 mg/m2 weekly times three with 1 week off until progressive disease or adverse effects prohibited further therapy. Doses were escalated or reduced based on previous cycle toxicity.Results. Twenty-seven patients were entered into the trial. One patient never received the drug and 1 patient was inevaluable for response. A median of two cycles were administered to each patient (range: 1–7 cycles). The overall response rate (two partial responses) was 8% with 21% of patients having stable disease. The median progression-free interval was 1.9 months (range: 0.5–9.0) and overall survival was 4.9 months (range: 1.5–16.3). Two patients had grade 4 neutropenia; 1 patient had grade 4 anemia. The median WBC nadir in the 13 patients experiencing any leukopenia was 2300/μl (range: 400–3800). There was only one episode of grade 4 gastrointestinal toxicity.Conclusions. Gemcitabine as a single agent demonstrated minimal antitumor activity in previously treated patients with squamous cell cancer of the uterine cervix. Since gemcitabine in the dose and schedule employed is known to potentiate the cytotoxicity of cisplatin and radiotherapy (the current standard therapies for this disease), further development of gemcitabine would only be indicated in combination with these treatment modalities.

Gemcitabine in the treatment of ovarian cancer

Gemcitabine in the treatment of ovarian cancer