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Posts Tagged ‘ANTINEOPLASTIC agents’

Evaluation of anti-emetic use in chemotherapy-induced nausea and vomiting in a third-world country (lebanon)






Rationale In Lebanon, the appropriateness of anti-emetic use is questionable in large measure because of the absence of published multicentre trials. Aim and objectives To evaluate the extent of appropriateness of anti-emetic use in patients on chemotherapy among several Lebanese hospitals. Appropriateness of chemotherapy-induced nausea and vomiting (CINV) prophylaxis was determined as per National Comprehensive Cancer Network guidelines. Methods A multicentre, cross-sectional study was conducted over a 3-month period. Data were collected from medical charts of cancer patients. The main outcome measure was to evaluate the appropriateness of prophylactic use of anti-emetics in CINV in terms of selected drug regimen, dosage and route of administration, and to investigate the role of several pre-specified variables (including hospital type and size, type of insurance coverage and patient-related factors) in influencing the appropriateness of anti-emetic practice. Results A total of 493 patients’ forms were analysed. The median age was 58.8 ± 13.9 years, 290 (58.8%) patients were female. Around 211 (42.8%) patients received inappropriate anti-emetic regimen, and only 17 (6%) patients of those receiving appropriate regimen received the appropriate dose, and just 55 (19.5%) patients were treated for the appropriate duration. Factors that may affect the relative effectiveness of treatment were identified. Conclusion This study reflected substantial flaws in CINV prophylaxis practice in Lebanon which should alert health care professionals of the adverse consequences resulting from non-adherence to guidelines. Our study also highlighted areas for improvement and suggested recommendations in order to minimize patient risk and optimize safe and effective CINV management. [ABSTRACT FROM AUTHOR]


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Development and economic trends in cancer therapeutic drugs in the uk from 1955 to 2009

Over the past decade, 23 new cancer treatment drugs have been introduced, many have brought major benefits to patient care, whilst others have maintained clinical benefits with reduced toxicity. In this article, the historical trends in drug numbers, therapeutic classification, and treatment costs have been reviewed. Drugs are classified by years of introduction, therapeutic classification, and an assessment of relative treatment cost using a contemporary ‘standard’ treatment compared with the relevant UK GDP per capita. Prior to 1960, there were 5 cancer drugs available, 2 new drugs were introduced in the 1960s, 18 in the 1970s, 14 in the 1980s, 24 in the 1990s, and 23 in the past decade. Prior to 1975, all the cancer treatments were classical cytotoxic agents. Since then, there have been 17 hormonal agents, 6 monoclonal antibodies, and 7 targeted therapies. The number of new classical cytotoxic drugs has declined dramatically with only one new agent in the past decade. The new drugs have become increasingly expensive relative to average GDP, with an average standard course of treatment with a new non-hormonal agent costing 34% of per capita GDP in 1995–1999, 53% in 2000–2004, and 67% in 2005–2009. In contrast, the cost of new hormonal agents introduced has remained at lower levels, with 6-month treatment with Degarelix, the newest hormonal agent, costing 3.8% of per capita GDP in 2009. The data in this article may be of value to those interested in the history of cancer treatment development and associated economic issues.

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A pharmacoeconomic modeling approach to estimate a value-based price for new oncology drugs in europe

Background. Several European governments have recently mandated price cuts in drugs to reduce health care spending. However, such measures without supportive evidence may compromise patient care because manufacturers may withdraw current products or not launch new agents. A value-based pricing scheme may be a better approach for determining a fair drug price and may be a medium for negotiations between the key stakeholders. To demonstrate this approach, pharmacoeconomic (PE) modeling was used from the Spanish health care system perspective to estimate a value-based price for bevacizumab, a drug that provides a 1.4-month survival benefit to patients with metastatic colorectal cancer (mCRC). The threshold used for economic value was three times the Spanish per capita GDP, as recommended by the World Health Organization (WHO).Methods. A PE model was developed to simulate outcomes in mCRC patients receiving chemotherapy ± bevacizumab. Clinical data were obtained from randomized trials and costs from a Spanish hospital. Utility estimates were determined by interviewing 24 Spanish oncology nurses and pharmacists. A price per dose of bevacizumab was then estimated using a target threshold of €78,300 per quality-adjusted life year gained, which is three times the Spanish per capita GDP.Results. For a 1.4-month survival benefit, a price of €342 per dose would be considered cost effective from the Spanish public health care perspective. The price may be increased to €733 or €843 per dose if the drug were able to improve patient quality of life or enhance survival from 1.4 to 3 months.Conclusions. This study demonstrated that a value-based pricing approach using PE modeling and the WHO criteria for economic value is feasible and perhaps a better alternative to government mandated price cuts. The former approach would be a good starting point for opening dialog between European government payers and the pharmaceutical industry.

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Once daily busulfan cyclophosphamide is well tolerated and effective as a preparative regimen for allogeneic hematopoietic stem cell transplant

We report a retrospective review of our institutional data using once daily intravenous (IV) busulfan (Bu) and cyclophosphamide (Cy) and total body irradiation (TBI)/Cy in patients who received allogeneic hematopoietic stem cell transplant (HCT) from January 2000 to December 2006. Bu 3.2 mg/kg IV once daily × 4 days followed by Cy 60 mg/kg IV daily × 2 days was given to 42 patients. Cy 60 mg/kg IV daily for 2 days and fractionated TBI 1200 cGy delivered over 3 days was given to 60 patients. Veno-occlusive disease developed in two patients in the once daily BuCy group and no patients in the TBI/Cy group. The once daily BuCy group had significantly less transplant-related mortality (TRM) than the TBI/Cy group at 100 days (p = 0.047) and better overall survival at 1 year (p = 0.01). This review demonstrates once daily IV BuCy and allogeneic HCT is well tolerated with no unexpected TRM or differences in clinical outcomes.

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The phaseal® system: impact of its use on workplace contamination and duration of chemotherapy preparation

Purpose. The primary objective of this study was to compare the levels of environmental contamination before and after the introduction of PhaSeal® (closed-system drug transfer device) in two hospital pharmacies. Our secondary objective was to assess the impact of the device on the duration of drug preparation compared to procedures involving the use of needles and syringes.Methods. The study involved two French hospitals, which prepared antineoplastic chemotherapy using a biological safety cabinet and an isolator. Five skilled pharmacy technicians at each hospital prepared a total of 100 chemotherapy preparations using the standard procedure and 100 using the PhaSeal® system. To control for possible contamination occurring in the course of the procedure, we used fluorescein which becomes fluorescent when exposed to UV light. To reply the second objective, we timed the duration of the different steps of the manipulation.Results. Our findings showed a major reduction in the contamination of the work environment when using the PhaSeal® system for drug preparation. Reduction rates higher than 93% were obtained, whatever the type of protection used. On the duration of preparation, our results indicate that this duration would be approximately 1 h longer for the preparation of 100 samples.Conclusion. In conclusion, this study clearly establishes the benefit of using PhaSeal® for protecting the staff members who work with hazardous agents. It also indicates that the duration of drug preparation is not impacted by the use of the system.

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Sampling and mass spectrometric analytical methods for five antineoplastic drugs in the healthcare environment

Context. Healthcare worker exposure to antineoplastic drugs continues to be reported despite safe handling guidelines published by several groups. Sensitive sampling and analytical methods are needed so that occupational safety and health professionals may accurately assess environmental and biological exposure to these drugs in the workplace.Objective. To develop liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analytical methods for measuring five antineoplastic drugs in samples from the work environment, and to apply these methods in validating sampling methodology. A single method for quantifying several widely used agents would decrease the number of samples required for method development, lower cost, and time of analysis. Methods for measuring these drugs in workers’ urine would also be useful in monitoring personal exposure levels.Results. LC-MS/MS methods were developed for individual analysis of five antineoplastic drugs in wipe and air sample media projected for use in field sampling: cyclophosphamide, ifosfamide, paclitaxel, doxorubicin, and 5-fluorouracil. Cyclophosphamide, ifosfamide, and paclitaxel were also measured simultaneously in some stages of the work. Extraction methods for air and wipe samples were developed and tested using the aforementioned analytical methods. Good recoveries from the candidate air and wipe sample media for most of the compounds, and variable recoveries for test wipe samples depending on the surface under study, were observed. Alternate LC-MS/MS methods were also developed to detect cyclophosphamide and paclitaxel in urine samples.Conclusions. The sampling and analytical methods were suitable for determining worker exposure to antineoplastics via surface and breathing zone contamination in projected surveys of healthcare settings.

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Malignant pleural mesothelioma

Purpose. The etiology, diagnosis, staging, and management of malignant pleural mesothelioma (MPM) are reviewed, with an emphasis on clinical trials of newer approaches to first-line, second-line, and adjuvant chemotherapy. Summary. In the past decade, more effective chemotherapy regimens have been developed for patients with MPM, a rapidly progressing disease linked to a history of asbestos exposure in about 70% of cases. Patients with MPM often require multimodal treatment with surgery, radiotherapy, and adjuvant or neoadjuvant (presurgical) chemotherapy. The current standard of first-line chemotherapy for MPM is cisplatin or carboplatin in combination with pemetrexed, an antifolate compound that has been shown to increase the cytotoxic effects of platinum-based drugs. In Phase II and III clinical trials, combination therapy with pemetrexed and either cisplatin or carboplatin yielded some of the highest rates of tumor response (21-41%) and overall survival (about 12-14 months) reported to date. Dual-agent neoadjuvant chemotherapy (cisplatin plus gemcitabine or pemetrexed) followed by radical surgery with or without radiotherapy has been reported to yield median survival of up to 23-29 months in small clinical trials, but larger randomized controlled studies are needed to better define the role of neoadjuvant therapy in MPM management. Other chemotherapeutic agents that have been used against MPM, with variable results, include gemcitabine, vinorelbine, taxanes, anthracyclines, and molecular-targeted agents. Conclusion. Treatment approaches for MPM include surgery, radiation, and systemic chemotherapy. MPM carries a poor prognosis, but recent studies of pemetrexed and platinum analogue combination therapies have demonstrated improved response rates over other treatments. [ABSTRACT FROM AUTHOR]

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Differentiation syndrome in patients with acute promyelocytic leukemia

Objective. To review the pathophysiology, risk factors, and management of differentiation syndrome (DS) associated with acute promyelocytic leukemia (APL).Data source. A MEDLINE search was conducted (1977–November 2010) using the terms APL, DS, all-trans retinoic acid (ATRA), retinoic acid syndrome, and arsenic trioxide (ATO).Methods of study selection. English articles identified from the MEDLINE search were evaluated.Data extraction and synthesis. With ATRA, ATO, and chemotherapy, a complete remission is achievable for most newly diagnosed APL patients. However, treatment with the differentiating agents, ATRA and ATO, can lead to the development of DS. Signs and symptoms of this syndrome include hyperleukocytosis and cardiorespiratory compromise. Severe complications can develop, if DS is not recognized early and treated promptly with corticosteroids. In addition, patients with a high white blood cell count at diagnosis may benefit from prophylactic steroids.Conclusions. Early recognition and prompt initiation of corticosteroids are key factors in the management of DS. Healthcare professionals need to be familiar with this complication which can arise from differentiation agents.

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Selective inhibition of extracellular signal-regulated kinases 1/2 blocks nerve growth factor to brain-derived neurotrophic factor signaling and suppresses the development of and reverses already established pain behavior in rats

Abstract: Brain-derived neurotrophic factor (BDNF) plays a key role in the development of pathological pain. Although it is known that nerve growth factor (NGF) induces BDNF mRNA through extracellular signal-regulated kinases (ERK), whether ERK1/2 or ERK5, two closely related members of the ERK family, mediate this signal is still unclear because classical MEK inhibitors block both pathways. We studied the involvement of ERK-signaling in NGF induction of BDNF in PC12 cells, cultured dorsal root ganglia neurons, and in rats subjected to neuropathic pain models using ERK1/2- and ERK5-specific tools. Selective activation of ERK1/2 upregulated BDNF mRNA in PC12 cells, whereas selective ERK5 activation did not. AZD6244, a potent selective inhibitor of ERK1/2 activation, blocked NGF induction of BDNF mRNA in vitro suggesting that NGF induction of BDNF is mediated by ERK1/2. siRNA experiments indicated that both ERK1 or ERK2 can signal suggesting that both pathways must be blocked to prevent NGF-induced increase in BDNF mRNA. I.p. injection of AZD6244 prevented the development of pain in rats subjected to the chronic constriction injury and reversed already established pain in the spared nerve injury model. Immunohistochemical studies showed decreased phospho-ERK1/2-immunoreactivity in dorsal root ganglia and BDNF immunoreactivity in ipsilateral spinal dorsal horn in the drug-treated rats. Our results suggest the possible use of AZD6244, already in human clinical trials as an anticancer agent, for the treatment of pathological pain. [Copyright &y& Elsevier]

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Synergistic antitumor effect of adenovirus-mediated hing4 gene therapy and 125i radiation therapy on pancreatic cancer

Abstract: Pancreatic cancer has a poor prognosis, even with surgery. ING4 is a member of the inhibitor of growth (ING) tumor suppressor family that has potent inhibitory effects on a variety of tumors; meanwhile, radiotherapy is a common adjunctive therapy for pancreatic cancer. Prior to this study, the effectiveness of a combination of ING4 gene-therapy and radiotherapy against pancreatic cancer had been unknown. In this study, we demonstrated that either ING4 or 125I radiotherapy treatment could induce Panc-1 pancreatic cancer cell growth suppression and apoptosis in vitro. Furthermore, both treatments inhibited tumor growth and angiogenesis of Panc-1 pancreatic cancer subcutaneously xenografted in vivo. Moreover, the combination therapy had a synergistic effect. [Copyright &y& Elsevier]

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