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Sample records for amifostine

  1. Has the outlook improved for amifostine as a clinical radioprotector?

    Science.gov (United States)

    Lindegaard, J C; Grau, C

    2000-11-01

    Amifostine has recently been approved for clinical radiotherapy as a protector against irradiation-induced xerostomia. It is our aim to review the outlook for using amifostine as a general clinical radioprotector. Protection against X-rays is mainly obtained by the scavenging of free radicals. The degree of protection is therefore highly dependent on oxygen tension, with protection factors ranging from 1 to 3. Maximal protection is observed at physiological levels of oxygenation. A great variability in protection has also been observed between different normal tissues. Some tissue, like brain, is not protected while salivary glands and bone marrow may exhibit a three-fold increase in radiation tolerance. Amifostine is dephosphorylized to its active metabolite by a process involving alkaline phosphatase. Due to lower levels of alkaline phosphatase in tumor vessels, amifostine is marketed as a selective protector of normal tissue and not tumors. However, the preclinical investigations concerning the selectivity of amifostine are controversial and the clinical studies are sparse and do not have the power to evaluate the influence of amifostine on the therapeutic index. based on the present knowledge amifostine should only be used in experimental protocols and not in routine practice.

  2. Amifostine - a radioprotector in locally advanced head and neck tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schoenekaes, K.G.; Wagner, W. [Paracelsus-Strahlenklinik, Osnabrueck (Germany); Prott, F.J. [Muenster Univ. (Germany). Inst. fuer Strahlenonkologie

    1999-11-01

    Purpose: There are some preliminary informations about the beneficial use of amifostine in avoiding side effects in patients with head and neck tumors who underwent radiotherapy. Patients and method: Amifostine was given as daily intravenous application (500 mg) 10 to 15 minutes prior to radiotherapy in 20 patients. The results were compared with another collective of patients which was similar. Results: According to the WHO score mucositis became manifest in 10 patients (Grade I) and 4 patients (Grade II) in the amifostine group vs 9 patients (Grade II), 6 patients (Grade III) and 1 patient (Grade IV) in the control group. Xerostomia has been seen in 15 patients (Grade I) and 5 patients (Grade II) after administration of amifostine. Without the drug 2 patients suffered from xerostomia (Grade I), 8 patients (Grade II) and 8 patients (Grade III), respectively. Administering amifostine had been feasible and non problematic. Only a small rate of toxic side effects like nausea (11%) or emesis (4%) was documented. Conclusions: Amifostine is an effective radioprotector decreasing acute and late side effects in patients with head and neck tumors. (orig.) [German] Zielsetzung: Bisher gibt es nur wenige Informationen ueber den Nutzen von Amifostin bezueglich der Verminderung oder Vermeidung von Nebenwirkungen einer Radiatio bei Patienten mit Tumoren im HNO-Trakt. Patienten und Methode: Amifostin wurde als intravenoese Kurzinfusion mit einer Dosis von 500 mg zehn bis 15 Minuten vor der Bestrahlung bei 20 Patienten appliziert. Die unter Radiatio aufgetretenen Nebenwirkungen wurden nach WHO bzw. nach dem Oral Assessment Guide nach Eilers ausgewertet und mit einem entsprechenden historischen Kollektiv der Klinik verglichen. Ergebnisse: In der Amifostin-Gruppe wurde bei zehn Patienten eine Mukositis Grad I und bei vier Patienten eine Mukositis Grad II nach WHO beobachtet. Grad-III- und Grad-IV-Nebenwirkungen traten nicht auf. In der Kontrollgruppe waren dagegen bei neun

  3. Alteration of radiation-induced hematotoxicity by amifostine

    International Nuclear Information System (INIS)

    Momm, Felix; Bechtold, Christine; Rudat, Volker; Strnad, Vratislav; Tsekos, Alexander; Fischer, Karin; Henke, Michael

    2001-01-01

    Purpose: To investigate whether amifostine can reduce radiation hematotoxicity. Patients and Methods: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5x2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m 2 amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n=501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. Results: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10 3 /mm 3 to 5.8x10 3 /mm 3 (difference: 2.3x10 3 /mm 3 ). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. Conclusion: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study

  4. Amifostine - a radioprotector in locally advanced head and neck tumors

    International Nuclear Information System (INIS)

    Schoenekaes, K.G.; Wagner, W.; Prott, F.J.

    1999-01-01

    Purpose: There are some preliminary informations about the beneficial use of amifostine in avoiding side effects in patients with head and neck tumors who underwent radiotherapy. Patients and method: Amifostine was given as daily intravenous application (500 mg) 10 to 15 minutes prior to radiotherapy in 20 patients. The results were compared with another collective of patients which was similar. Results: According to the WHO score mucositis became manifest in 10 patients (Grade I) and 4 patients (Grade II) in the amifostine group vs 9 patients (Grade II), 6 patients (Grade III) and 1 patient (Grade IV) in the control group. Xerostomia has been seen in 15 patients (Grade I) and 5 patients (Grade II) after administration of amifostine. Without the drug 2 patients suffered from xerostomia (Grade I), 8 patients (Grade II) and 8 patients (Grade III), respectively. Administering amifostine had been feasible and non problematic. Only a small rate of toxic side effects like nausea (11%) or emesis (4%) was documented. Conclusions: Amifostine is an effective radioprotector decreasing acute and late side effects in patients with head and neck tumors. (orig.) [de

  5. The Effect of Amifostine on Submandibular Gland Histology after Radiation

    Directory of Open Access Journals (Sweden)

    Jacqueline C. Junn

    2012-01-01

    Full Text Available Background. The purpose of this study was to assess the effects of amifostine on submandibular gland histology in patients receiving chemoradiation therapy. Methods. We conducted a retrospective submandibular gland histologic slide review of HNSCC patients receiving chemoradiation for head and neck squamous cell carcinoma with three different levels of amifostine exposure. We used six scoring parameters: fatty replacement, lobular architecture degeneration, interstitial fibrosis, ductal degeneration, acinar degeneration, and inflammatory component presence. Results. Differences in gender, tumor stage, amifostine dose, age, number of days after neck dissection, and smoking history (pack years exposure were not significant between the three groups, although there was a difference between groups in the primary subsite (P=0.006. The nonparametric Cuzick's test for histologic parameters with varied amifostine treatment showed no significance among the three groups. Conclusions. Although patients did not receive a full dose of amifostine due to side effects, varying doses of amifostine had no apparent evident cytoprotective effects in three groups of cancer patients treated with primary chemoradiation.

  6. Pharmacokinetics of cisplatin with and without amifostine in tumour- bearing nude mice

    NARCIS (Netherlands)

    Korst, A.E.C.; Boven, E.; Sterre, M.L.T. van der; Fichtinger-Schepman, A.M.J.; Vijgh, W.J.F. van der

    1998-01-01

    Amifostine (Ethyol, WR-2721) is in use in the clinic as a protector against platinum-induced toxicities. We have previously reported that amifostine induced a potentiation of the antitumour activity of carboplatin in human ovarian cancer xenografts. An influence of amifostine on the pharmacokinetics

  7. Influence of amifostine on the pharmacokinetics of cisplatin in cancer patients

    NARCIS (Netherlands)

    Korst, A.E.C.; Sterre, M.L.T. van der; Gall, H.E.; Fichtinger-Schepman, A.M.J.; Vermorken, J.B.; Vijgh, W.J.F. van der

    1998-01-01

    The pharmacokinetics of cisplatin was investigated in 13 patients receiving 18 courses of cisplatin alone or in combination with amifostine to investigate the influence of amifostine (WR 2721; Ethyol) on the pharmacokinetics of cisplatin. Cisplatin was administered as a 1-h i.v. infusion, whereas

  8. Amifostine-induced fever: case report and review of the literature.

    Science.gov (United States)

    Boehme, Sabrina; Wilson, David B

    2004-01-01

    Amifostine, also known as WR-2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid), is an organic thiophosphate cytoprotective agent used to reduce the frequency of severe xerostomia in patients with cancer undergoing postoperative radiation of the head and neck. A 56-year-old Caucasian man who received concomitant chemotherapy and radiation for head and neck cancer developed fever concurrent with the administration of amifostine. To our knowledge, this is the first case report that demonstrates the occurrence of fever with low-dose amifostine therapy without the manifestation of accompanying rash or hypotension. Patients receiving amifostine who develop only fever should be evaluated for an adverse drug reaction, as well as for sepsis and fevers of neutropenia, and it may be necessary to discontinue the drug. Recognition of amifostine as the cause of this adverse event may prevent the cost and inconvenience of a hospital admission.

  9. Amifostine is a potent radioprotector of salivary glands in radioiodine therapy. Structural and ultrastructural findings

    International Nuclear Information System (INIS)

    Kutta, H.; Kampen, U.; Sagowski, C.; Brenner, W.; Bohuslavizki, K.H.; Paulsen, F.

    2005-01-01

    Background and purpose: salivary gland impairment following high-dose radioiodine treatment is well recognized. Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigates the radioprotective effects of amifostine in salivary glands of rabbits receiving high-dose radioiodine therapy so as to obtain deeper insight in changes on the cellular and ultrastructural level. Material and methods: a total of 20 rabbits were investigated. High-dose radioiodine therapy applying 1 GBq 131 I was performed in 16 animals. Eight of these 16 animals received 200 mg/m 2 body surface amifostine prior to high-dose radioiodine therapy. Four additional rabbits served as controls, two receiving amifostine, the other two no treatment at all. Subsequently, salivary glands (submandibular and parotid glands, respectively) of all animals were examined by light and transmission electron microscopy. Results: parenchymal damage of both parotid and submandibular glands, specially acinar structures comprising cell organelles and nuclei, of animals pretreated with amifostine was much less pronounced than in animals without amifostine pretreatment. Conclusion: the results indicate that parenchymal damage in salivary glands induced by high-dose radioiodine therapy can significantly be reduced by amifostine. Therefore, amifostine therapy may increase quality of life in patients with differentiated thyroid cancer after radioiodine treatment. (orig.)

  10. Amifostine is a potent radioprotector of salivary glands in radioiodine therapy. Structural and ultrastructural findings

    Energy Technology Data Exchange (ETDEWEB)

    Kutta, H. [Dept. of Anatomy, Christian Albrecht Univ. of Kiel (Germany); Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Univ. Hospital Hamburg-Eppendorf, Hamburg (Germany); Kampen, U. [Clinic of Nuclear Medicine, Christian Albrecht Univ. of Kiel (Germany); Sagowski, C. [Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Univ. Hospital Hamburg-Eppendorf, Hamburg (Germany); Brenner, W. [Clinic of Nuclear Medicine, Christian Albrecht Univ. of Kiel (Germany); Dept. of Nuclear Medicine, Univ. Hospital Hamburg-Eppendorf, Hamburg (Germany); Bohuslavizki, K.H. [Nuclear Medicine, Hamburg (Germany); Paulsen, F. [Dept. of Anatomy, Christian Albrecht Univ. of Kiel (Germany); Dept. of Anatomy and Cell Biology, Martin-Luther-Univ. of Halle-Wittenberg, Halle/Saale (Germany)

    2005-04-01

    Background and purpose: salivary gland impairment following high-dose radioiodine treatment is well recognized. Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigates the radioprotective effects of amifostine in salivary glands of rabbits receiving high-dose radioiodine therapy so as to obtain deeper insight in changes on the cellular and ultrastructural level. Material and methods: a total of 20 rabbits were investigated. High-dose radioiodine therapy applying 1 GBq {sup 131}I was performed in 16 animals. Eight of these 16 animals received 200 mg/m{sup 2} body surface amifostine prior to high-dose radioiodine therapy. Four additional rabbits served as controls, two receiving amifostine, the other two no treatment at all. Subsequently, salivary glands (submandibular and parotid glands, respectively) of all animals were examined by light and transmission electron microscopy. Results: parenchymal damage of both parotid and submandibular glands, specially acinar structures comprising cell organelles and nuclei, of animals pretreated with amifostine was much less pronounced than in animals without amifostine pretreatment. Conclusion: the results indicate that parenchymal damage in salivary glands induced by high-dose radioiodine therapy can significantly be reduced by amifostine. Therefore, amifostine therapy may increase quality of life in patients with differentiated thyroid cancer after radioiodine treatment. (orig.)

  11. [Prediction and bioinformatics analysis of human gene expression profiling regulated by amifostine].

    Science.gov (United States)

    Yang, Bo; Cai, Li-Li; Chi, Xiao-Hua; Lu, Xue-Chun; Zhang, Feng; Tuo, Shuai; Zhu, Hong-Li; Liu, Li-Hong; Yan, Jiang-Wei; Tuo, Chao-Wei

    2011-06-01

    Objective of this study was to perform bioinformatics analysis of the characteristics of gene expression profiling regulated by amifostine and predict its novel potential biological function to provide a direction for further exploring pharmacological actions of amifostine and study methods. Amifostine was used as a key word to search internet-based free gene expression database including GEO, affymetrix gene chip database, GenBank, SAGE, GeneCard, InterPro, ProtoNet, UniProt and BLOCKS and the sifted amifostine-regulated gene expression profiling data was subjected to validity testing, gene expression difference analysis and functional clustering and gene annotation. The results showed that only one data of gene expression profiling regulated by amifostine was sifted from GEO database (accession: GSE3212). Through validity testing and gene expression difference analysis, significant difference (p < 0.01) was only found in 2.14% of the whole genome (460/192000). Gene annotation analysis showed that 139 out of 460 genes were known genes, in which 77 genes were up-regulated and 62 genes were down-regulated. 13 out of 139 genes were newly expressed following amifostine treatment of K562 cells, however expression of 5 genes was completely inhibited. Functional clustering displayed that 139 genes were divided into 11 categories and their biological function was involved in hematopoietic and immunologic regulation, apoptosis and cell cycle. It is concluded that bioinformatics method can be applied to analysis of gene expression profiling regulated by amifostine. Amifostine has a regulatory effect on human gene expression profiling and this action is mainly presented in biological processes including hematopoiesis, immunologic regulation, apoptosis and cell cycle and so on. The effect of amifostine on human gene expression need to be further testified in experimental condition.

  12. Radiochemotherapy With Cetuximab, Cisplatin, and Amifostine for Locally Advanced Head and Neck Cancer: A Feasibility Study

    International Nuclear Information System (INIS)

    Koukourakis, Michael I.; Tsoutsou, Pelagia G.; Karpouzis, Antonios; Tsiarkatsi, Maria; Karapantzos, Ilias; Daniilidis, Vassilios; Kouskoukis, Constantinos

    2010-01-01

    Purpose: Radiotherapy (RT) combined with cisplatin or cetuximab is the standard of care for patients with locally advanced head/neck cancer (LA-HNC). The feasibility of radiochemotherapy with cisplatin and cetuximab, supported with amifostine, was herein investigated. Methods and Materials: Forty-three patients with LA-HNC were recruited. Conformal hypofractionated/accelerated RT with amifostine cytoprotection (2.7 Gy/fraction, 21 fractions in 4 weeks) was combined with cisplatin (30 mg/m 2 /week) and cetuximab (standard weekly regimen) therapy. The dose of amifostine was individualized according to tolerance. Results: A high daily amifostine dose (750-1,000 mg) was tolerated by 41.8% of patients, and a standard dose (500 mg) was tolerated by 34.9% of patients. A high amifostine dose was linked to reduced RT delays (p = 0.0003). Grade 3 to 4 (3-4) mucositis occurred in 7/43 (16.2%) patients, and fungal infections occurred in 18/43 (41.8%) patients. Radiation dermatitis was not aggravated. Interruption of cetuximab due to acneiform rash was necessary in 23.3% of patients, while amifostine-related fever and rash were not observed. Severe late radiation sequelae consisted of laryngeal edema (9% laryngeal cases) and cervical strictures (33% of hypopharyngeal cases). Good salivary function was preserved in 6/11 (54.5%) nasopharyngeal cancer patients. The complete response rate was 68.5%, reaching 77.2% in patients with minor radiotherapy delays. The 24-month local control and survival rates were 72.3% and 91%, respectively (median follow-up was 13 months.). Conclusions: In this feasibility study, weekly administration of cisplatin and cetuximab was safely combined with accelerated RT, supported with amifostine, at the cost of a high incidence of acneiform rash but a reduced incidence of amifostine-related fever/rash. A high daily dose of amifostine allows completion of therapy with minor delays.

  13. A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

    International Nuclear Information System (INIS)

    Anne, Pramila Rani; Machtay, Mitchell; Rosenthal, David I.; Brizel, David M.; Morrison, William H.; Irwin, David H.; Chougule, Prakash B.; Estopinal, Noel C.; Berson, Anthony; Curran, Walter J.

    2007-01-01

    Purpose: Intravenous amifostine 200 mg/m 2 reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. Patients and Methods: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of ≥Grade 2 acute xerostomia. Results: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of ≥Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of ≥Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. Conclusions: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients

  14. Design and evaluation of biodegradable enteric microcapsules of amifostine for oral delivery.

    Science.gov (United States)

    A, Gula; Ren, Lei; Zhou, Zhe; Lu, Dandan; Wang, Shengqi

    2013-09-10

    Amifostine is the first FDA approved cytoprotective and chemoprotective agent in the treatment of cancer. However, it is not used widely because of its ineffectiveness when administered orally. The objective of this study was to prepare and evaluate the radioprotective efficacy of orally active amifostine enteric microcapsules (amifostine mc). The microcapsules were prepared by spray drying technique using Eudragit L100-55, and the yield was more than 80%. The particle size and surface morphology were determined by particle analyzer and scanning electron microscopy. Thermal characterization and infrared spectroscopy were evaluated as well. In vitro release assay found that more than 60% amifostine was released during the first 4h and the cumulative release ratio was up to approximately 90% in 24h at 37°C. The radioprotective efficacy was determined by 30-day survival study in mice acutely exposed to 6 Gy γ-ray irradiation. The results showed that all dose groups of amifostine microcapsules could significantly improve survival animal numbers and time. Furthermore, tissue distribution studies indicated the concentrations of the active metabolite WR-1065 in mice tissues of microcapsule group were higher than that of oral amifostine group at 180 min (pmicrocapsules provided effective radioprotection compared to the bulk drug. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Ultrasensitive detection of amifostine and alkaline phosphatase based on the growth of CdS quantum dots.

    Science.gov (United States)

    Na, Weidan; Liu, Siyu; Liu, Xiaotong; Su, Xingguang

    2015-11-01

    In this study, we reported a simple and sensitive fluorescence nanosensor for rapid detection of amifostine and alkaline phosphatase (ALP). The novel nanosensor was based on the fluorescence "turn on-off" of CdS quantum dots (QDs). Firstly, Cd(2+) cation could react with S(2-) anion to generate fluorescent CdS QDs in the presence of amifostine. The fluorescence (FL) intensity of amifostine-capped CdS QDs (Amifostine-CdS QDs) was increased with the increasing amounts of amifostine, and could be used for amifostine detection. However, amifostine could be converted to 2-(3-aminopropylamino) ethanethiol (WR1065) in the presence of ALP based on the dephosphorylation of ALP. Under the optimum conditions, the affinity of WR1065 to CdS QDs was weaker than that of amifostine. Therefore the new generation of WR1065-CdS QDs would reduce the FL intensity with the increase of ALP concentration, and the fluorescence of CdS QDs was turn off. The metabolic process of amifostine in the presence of alkaline phosphatase could be also studied via the change of FL intensity of CdS QDs. The present method was cost-effective, convenient, and does not require any complicated synthetic procedures. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly: A prospective randomized study in squamous cell head and neck cancer

    NARCIS (Netherlands)

    Jellema, Anke Petra; Slotman, Ben J.; Muller, Martin J.; Leemans, C. Rene; Smeele, Ludi E.; Hoekman, Klaas; Aaronson, Neil K.; Langendijk, Johannes A.

    2006-01-01

    BACKGROUND: The main objective of this study was to investigate whether nondaily intravenous administration of amifostine was as effective as daily intravenous administration with regard to the reduction of the incidence of Grade 2 or greater xerostomia in patients with head and neck cancer.

  17. Assessment of the Cytoprotective Efficacy of Amifostine with Quantitative Salivary Gland Scintigraphy

    Directory of Open Access Journals (Sweden)

    Bilgehan Karadayı

    2005-01-01

    Full Text Available The main objective of our study was to assess and confirm the radioprotective effect of amifostine in protecting major salivary glands with dynamic quantitative scintigraphic evaluation.The study design was non-randomized clinical trial. There were 26 patients with head and neck cancer who receive primary or adjuvant radiotherapy in the head and neck region. Amifostine administrations were done before radiotherapy in one group while the control group did not take the drug. The primary end-point was wash-out rate as the quantitative scintigraphic parameter and changing patterns after radiotherapy were compared. Parotid wash-out rate showed some healing at the 3rd month of radiotherapy in the amifostine group, but not in the control group. Submandibular wash-out rate showed some worsening at the 3rd month of radiotherapy in the control group, but not in the amifostine group. Radioprotective effect of amifostine in major salivary glands can be observed with the testing tool of dynamic quantitative salivary gland scintigraphy.

  18. Animal experimental studies on the modification of radiogenic mucositis enoralis through amifostin

    International Nuclear Information System (INIS)

    Fleischer, G.; Doerr, W.

    2004-01-01

    The purpose of the present study was to quantify the protective effect of amifostin administered intravenously and subcutaneously in conjunction with one-time irradiation and fractionated irradiation regimes. Ulceration of the mouse lingual mucous membrane equivalent to RTOG/EORTC stage III confluent mucositis served as a clinically relevant parameter. In summary it can be said that the mucoprotective effect of amifostin is clearly dependent on when it is given. It is only effective when administered at the start of fractionated irradiation. It has no effect when administered at a later time, possibly even masking the effect of earlier doses. Amifostin administered subcutaneously, a mode which has been associated with markedly fewer side-effects in clinical studies, and after a suitably adapted time interval following irradiation is just as effective as when it is injected intravenously [de

  19. Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

    Science.gov (United States)

    Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

    2018-03-19

    Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

  20. Effect of amifostine on patient assessed clinical benefit in irradiated head and neck cancer

    International Nuclear Information System (INIS)

    Wasserman, Todd; Mackowiak, John I.; Brizel, David M.; Oster, Wolfgang; Zhang, Jianliang; Peeples, Patricia J.; Sauer, Rolf

    2000-01-01

    Purpose: To determine if head and neck (H/N) cancer patients receiving daily amifostine during radiation therapy (RT) experienced clinical benefit (improvement in their ability to carry out normal functions with reduced discomfort) compared to nonamifostine treated patients. Methods and Materials: This was an open-label, multi-institutional randomized trial in 303 H/N cancer patients treated with RT +amifostine. Clinical benefit was measured using an 8-item validated Patient Benefit Questionnaire (PBQ) during and up to 11 months after RT. Results: 301 patients completed one or more PBQ assessments. Amifostine patients had significantly better PBQ scores (p < 0.05) than controls. The improvement in PBQ scores was most significant during chronic xerostomia. Conclusions: Amifostine use results in improved Patient Benefit Questionnaire (PBQ) scores, which is indicative of improved oral toxicity related outcomes and improved clinical benefit. Less oral toxicity should lead to preservation of late dental and oral health, and improvements in activities such as diet, nutrition, and sleep

  1. Effect of amifostine on sperm DNA fragmentation and testes after radioiodine treatment

    Directory of Open Access Journals (Sweden)

    Sen Cigdem Cebi

    2017-12-01

    Full Text Available Introduction: Radioactive iodine (RAI is commonly used for the treatment of hyperthyroidism caused by Graves’ disease or thyroid nodules. However, information available on the impact of RAI therapy on male gonadal function is scarce. This study aimed to determine any possible damage to testicular tissue and sperm quality caused by RAI therapy, and the radioprotective effect of amifostine against such damage.

  2. Systematic review of amifostine for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Nicolatou-Galitis, Ourania; Sarri, Triantafyllia; Bowen, Joanne; Di Palma, Mario; Kouloulias, Vassilios E.; Niscola, Pasquale; Riesenbeck, Dorothea; Stokman, Monique; Tissing, Wim; Yeoh, Eric; Elad, Sharon; Lalla, Rajesh V.

    The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. A systematic review was conducted by the Mucositis Study Group of

  3. Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Musto, Pellegrino; Santini, Valeria; Balestri, Francesca

    2002-01-01

    Twelve patients with myelodysplasia were treated with amifostine plus recombinant human erythropoietin (rHuEpo) for 6 weeks. A complete erythroid response was obtained in 2/12(16.6%) and a partial response in 4/12 (33.3%). Two of 8 patients with a platelet count 100 x 10(9)/L had a complete...

  4. Amifostine for salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer.

    Science.gov (United States)

    Ma, Chao; Xie, Jiawei; Chen, Qingfeng; Wang, Guoming; Zuo, Shuyao

    2009-10-07

    Radioactive iodine treatment for differentiated thyroid cancer possibly results in xerostomia. Amifostine has been used to prevent the effects of irradiation to salivary glands. To date, the effects of amifostine on salivary glands in radioactive iodine treated differentiated thyroid cancer remain uncertain. To assess the effects of amifostine on salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer. Studies were obtained from computerized searches of MEDLINE, EMBASE, The Cochrane Library and paper collections of conferences held in Chinese. Randomised controlled clinical trials and quasi-randomised controlled clinical trials comparing the effects of amifostine on salivary glands after radioactive iodine treatment for differentiated thyroid cancer with placebo and a duration of follow up of at least three months. Two authors independently assessed risk of bias and extracted data. Two trials with 130 patients (67 and 63 patients randomised to intervention versus control) were included. Both studies had a low risk of bias. Amifostine versus placebo showed no statistically significant differences in the incidence of xerostomia (130 patients, two studies), the decrease of scintigraphically measured uptake of technetium-99m by salivary or submandibular glands at twelve months (80 patients, one study), and the reduction of blood pressure (130 patients, two studies). Two patients in one study collapsed after initiation of amifostine therapy and had to be treated by withdrawing the infusion and volume substitution. Both patients recovered without sequelae. Meta-analysis was not performed on the function of salivary glands measured by technetium-99m scintigraphy at three months after high dose radioactive iodine treatment due to the highly inconsistent findings across studies (I(2) statistic 99%). None of the included trials investigated death from any cause, morbidity, health-related quality of life or costs. Results from two randomised

  5. Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models

    Directory of Open Access Journals (Sweden)

    Joanna Klubo-Gwiezdzinska

    2017-09-01

    Full Text Available Background: Amifostine is a potent scavenger of reactive oxygen species that is used for the salivary gland protection during therapy with radioactive iodine for thyroid cancer. There are no data on the potential effect of amifostine on thyroid cancer cells. Methods: We investigated the effects of the active form of amifostine (WR-1065 on the response of thyroid cancer cells to treatment with DNA-damaging agents. WR-1065 was examined in human thyroid cancer cell lines (FTC133, TPC1, BCPAP and C643 and embryonic fibroblast cells NIH3T3. DNA damage was induced by exposure to H2O2 (0.1 mM, by treatment with the radiomimetic neocarzinostatin (NCS 250 ng/mL and by γ-radiation (6 Gy. DNA damage, cell viability and apoptosis were examined. Results: We demonstrated the selective action of WR-1065 (0.1 mM, which prevented oxidative stress–induced DNA damage in fibroblasts, but did not protect thyroid cancer cells from DNA damage and apoptosis documented by caspase-3 and PARP cleavage after exposure to H2O2, NCS and γ-radiation. Prolonged exposure to WR-1065 (0.1 mM for 24 h was toxic for thyroid cancer cells; this treatment decreased the number of viable cells by 8% in C643 cells, 47% in TPC cells, 92% in BCPAP cells and 82% in FTC 133 cells. The cytotoxic effects of WR-1065 were not associated with induction of apoptosis. Conclusions: Our data show that amifostine has no protective effect on thyroid cancer cells against DNA-damaging agents in vitro and suggest that amifostine will not attenuate the efficacy of radioiodine treatment in patients with thyroid cancer.

  6. Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer

    International Nuclear Information System (INIS)

    Antonadou, Dosia; Pepelassi, Marizenia; Synodinou, Maria; Puglisi, Maria; Throuvalas, Nicolas

    2002-01-01

    Purpose: To determine the prophylactic properties of amifostine against acute and late toxicities from radiochemotherapy in patients with head-and-neck cancer. Methods and Materials: Fifty patients were randomized to receive conventional radiotherapy (RT) (2-Gy fractions, 5 days weekly, to a total of 60-74 Gy, depending on the tumor localization and TNM classification) and carboplatin (90 mg/m 2 infusion once per week before RT). Amifostine (300 mg/m 2 ) was administered in the study group only 15-30 min before RT for 6-7.5 weeks. The primary study end point was the grading of acute and late nonhematologic toxicities (mucositis, dysphagia, xerostomia) induced by radiochemotherapy. Secondary end points included treatment duration, hematologic toxicity, and clinical outcome. Results: The treatment duration was significantly shorter in the amifostine-treated group (p=0.013), because treatment interruptions were more frequent in the control group. Acute toxicities (mucositis and dysphagia) were less severe in the amifostine-treated group. By Week 3, all in the control group experienced Grade 2 mucositis compared with only 9% in the amifostine-treated group (p<0.0001). By Week 5, 52.2% of the patients in the control group experienced Grade 4 mucositis compared with 4.5% in the amifostine-treated group (p=0.0006). Similar results were obtained for dysphagia. At 3 months of follow-up, only 27% of patients in the study group experienced Grade 2 xerostomia compared with 73.9% in the control group (p=0.0001). Eighteen months after cessation of therapy, the proportion of patients with Grade 2 xerostomia was 4.5% vs. 30.4% for each respective treatment group (p=0.047). Cytoprotection with amifostine did not affect treatment outcome, with 90.9% complete responses in the amifostine-treated group compared with 78.3% in the control group (p=0.414). Conclusion: Amifostine was effective in reducing mucositis and dysphagia resulting from radiochemotherapy in patients with head

  7. A pilot study of topical intrarectal application of amifostine for prevention of late radiation rectal injury

    International Nuclear Information System (INIS)

    Ben-Josef, Edgar; Han, Sue; Tobi, Martin; Shaw, Leslie M.; Bonner, Heather S.; Vargas, Barbara J.; Prokop, Sharon; Stamos, Beth; Kelly, Laura; Biggar, Sandra; Kaplan, Irving

    2002-01-01

    Purpose: Clinical symptomatic late injury to the rectal wall occurs in about one-third of patients with prostate cancer treated with external beam irradiation. Reducing the physical dose to the anterior rectal wall without a similar reduction in the posterior peripheral zone is difficult because of the proximity of the prostate to the anterior rectal wall. On the basis of our previous observations in an animal model that intrarectal application of amifostine resulted in very high concentrations of amifostine and its active metabolite WR-1065 in the rectal wall, a Phase I dose-escalation clinical trial was undertaken. Methods and Materials: Twenty-nine patients with localized prostate cancer were accrued. Eligibility criteria included histologically confirmed adenocarcinoma, Karnofsky performance status ≥70, and no pelvic lymphadenopathy or distant metastases. The total dose to the prostate was 70.2 Gy in 20 patients and 73.8 Gy in 9 patients. Therapy was delivered using a 4-field technique with three-dimensional conformal planning. Amifostine was administered intrarectally as an aqueous solution 30 min before irradiation on the first 15 days of therapy. Amifostine was escalated in cohorts from 500 to 2500 mg. Proctoscopy was performed before therapy and at 9 months after completion. Most patients underwent repeat proctoscopy at 18 months. On Days 1 and 10 of radiotherapy, serum samples were collected for pharmacokinetic studies. The clinical symptoms (Radiation Therapy Oncology Group scale) and a proctoscopy score were assessed during follow-up. Results: All patients completed therapy with no amifostine-related toxicity at any dose level. The application was feasible and well tolerated. No substantial systemic absorption occurred. With a median follow-up of 26 months, 9 patients (33%) developed rectal bleeding (8 Grade 1, 1 Grade 2). At 9 months, 16 and 3 patients developed Grade 1 and Grade 2 telangiectasia, respectively. This was mostly confined to the anterior

  8. Effects of insulin-like growth factor-1 (IGF-1) and amifostine in spinal cord reirradiation

    International Nuclear Information System (INIS)

    Nieder, C.; Andratschke, N.; Price, R.E.; Rivera, B.; Ang, K. Kian

    2005-01-01

    Purpose: To test whether insulin-like growth factor-1 (IGF-1) and amifostine modulate the reirradiation tolerance of rat cervical spinal cord. Initial experiments by the authors' group suggested that administration of each agent alone significantly increased the median latent time to radiation myelopathy (RM) in previously unirradiated animals but did not change the dose-response relationship. Because of different modes of action, a follow-up study was undertaken to test the combined treatment. Material and Methods: The cervical spinal cord of 51 adult Fisher F-344 rats received a single fraction of 16 Gy, which corresponds to approximately 75% of the median paresis dose (ED 50 ), followed 5 months later by a second radiation dose, which ranged from 17 to 21 Gy. The study animals received a single intrathecal injection of 0.3 mg amifostine into the cisterna magna 30-60 min before reirradiation plus three subcutaneous doses of IGF-1 (700 μg) starting from 24 h before to 24 h after reirradiation. Control animals received saline injections via the same routes. Animals were followed until RM developed or until 12 months from reirradiation. Histopathologic examinations were performed post mortem. Results: No animals showed any neurologic abnormalities before reirradiation. RM occurred in controls versus treated rats after a mean latency of 218 versus 314 days (19 Gy; p=0.11) and 104 versus 186 days (21 Gy; p=0.002) from second dose (Figure 1). ED 50 was 18.2 versus 19.4 Gy (p=0.15; Figure 2). Treatment with IGF-1 and amifostine did not significantly influence the rates of tumor induction or intercurrent death. Conclusion: IGF-1 and amifostine significantly reduced RM rates after 21 Gy. The shift of the dose-response curve suggests an increase of the ED 50 for single-dose treatment by approximately 7%. Thus, brief therapeutic intervention might slightly decrease radiation-induced neurotoxicity in a retreatment situation. (orig.)

  9. Salivary gland protection by amifostine in high-dose radioiodine therapy of differentiated thyroid cancer

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    Bohuslavizki, K.H.; Klutmann, S.; Bleckmann, C.; Mester, J.; Clausen, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Dept. of Nuclear Medicine; Brenner, W.; Lassmann, S.; Henze, E. [Kiel Univ. (Germany). Clinic of Nuclear Medicine

    1999-02-01

    Quantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq I-131. Eight patients were treated with 500 mg/m{sup 2} amifostine prior to high-dose radioiodine treatment and compared retrospectively with 9 control patients. Xerostomia was graded according to WHO criteria. In 9 control patients high-dose radioiodine treatment significantly (p<0.01) reduced Tc-99m-pertechnetate uptake by 35.4{+-}22.0% and 31.7{+-}21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p=0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. (orig.) [Deutsch] Im Rahmen eines Heilversuchs wurde eine limitierte Anzahl von Patienten untersucht. Vor und drei Monate nach Gabe von 6 GBq I-131 wurde eine quantitative Speicheldruesenszintigraphie mit 100 bis 120 MBq Tc-99m-Pertechnetat an 17 Patienten mit differenzierten Schilddruesenkarzinomen durchgefuehrt. Acht Patienten erhielten vor Radiojodtherapie 500 mg/m{sup 2} Amifostin und wurden mit einer historischen Kontrollgruppe aus neun Patienten verglichen. Eine Xerostomie wurde nach WHO-Kriterien beurteilt. Die Patienten der Kontrollgruppe wiesen sowohl fuer die Glandulae parotides als auch fuer die Glandulae submandibulares eine signifikante Verminderung der Tc-99m-Pertechnetat-Aufnahme um 35,4{+-}22,0% bzw. 31,7{+-}21,1% als Zeichen einer Parenchymschaedigung auf. Bei drei dieser neuen Patienten fand sich eine Xerostomie Grad I (WHO). Im Gegensatz dazu konnte bei den mit Amifostin behandelten Patienten keine signifikante Verminderung der Parechymfunktion festgestellt werden (p=0,878). Dementsprechend wies keiner dieser Patienten eine Xerostomie auf. (orig.)

  10. Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study

    International Nuclear Information System (INIS)

    Trog, D.; Bank, P.; Wendt, T.G.; Koscielny, S.; Beleites, E.

    1999-01-01

    Background: In patients with loco-regionally advanced head and neck cancer conventionally fractionated radiotherapy alone results in poor loco-regional control and survival rates. Treatment intensification by simultaneous administration of cytotoxic drugs produces higher acute morbidity. Therefore chemical radioprotection of normal tissues may be of clinical benefit. Patients and Methods: In a pilot study patients with advanced nonresectable head neck cancer treated with conventionally fractionated radical radiotherapy (60 to 66 Gy total doses) and concomitantly given 5-fluorouracil as protracted venous infusion, 250 mg/sqm/24 h over the entire treatment period were given amifostine 300 mg absolutely before each fraction. Acute treatment related mobidity was scored according to CTC classification and loco-regional control and survival rates were estimated. Comparison was made with a historical control group of identical chemoradiation but without amifostine application. Results: Chemoradiation induced oral mucositis was delayed and showed significant lower degrees at all 10 Gy increments (p 0.05). No significant toxicity was recorded with respect to blood pressure, serum calcium, potassium, hematologic parameters, emesis, nausea or body weight loss. Progression free survival and overall survival probability at 2 years were not statistically different in both cohorts. Conclusion: Amifostine given before each fraction of radiotherapy over 6 weeks has no cumulative toxicity, was well tolerated and may reduce treatment induced oral mucositis. No tumor protective effect was observed. (orig.) [de

  11. The potential influence of cell protectors for dose escalation in cancer therapy: an analysis of amifostine

    International Nuclear Information System (INIS)

    McCumber, Linda M.

    2004-01-01

    The attempt to increase the therapeutic ratio in an effort to improve survival or quality of life is the goal of modern cancer therapy. It is commonly accepted that local and systemic tumor control would increase if the dose intensity of antineoplastic drugs, radiation therapy, or the combination were increased. Radiation dose escalation using intensity-modulated radiation therapy (IMRT), accelerated or hypofractionated radiation schemes, and multidrug chemotherapy regimens are being used to try to increase tumor kill while inflicting minimal injury to normal tissue. Modern chemoradiation techniques have led to improved local regional control and increased cure rates, but the potentially severe and debilitating adverse effects of the therapies prevent them from reaching the ultimate goal of curing the disease while leaving the patient with a good quality of life. Cell protectants such as amifostine function by reducing the effects of therapy on normal cells while maintaining tumor sensitivity to the therapy. In various studies, amifostine has been analyzed and appears to be a potentially powerful adjuvant to current cancer therapy. Administering amifostine may allow dose escalation with less or equal risk to surrounding normal tissues. This could improve therapeutic efficacy, survival, and quality of life for cancer patients

  12. Intrarectal amifostine suspension may protect against acute proctitis during radiation therapy for prostate cancer: A pilot study

    International Nuclear Information System (INIS)

    Singh, Anurag K.; Menard, Cynthia; Guion, Peter; Simone, Nicole L.; Smith, Sharon; Crouse, Nancy Sears; Godette, Denise J.; Cooley-Zgela, Theresa; Sciuto, Linda C.; Coleman, Jonathan; Pinto, Peter; Albert, Paul S.; Camphausen, Kevin; Coleman, C. Norman

    2006-01-01

    Purpose: Our goal was to test the ability of intrarectal amifostine to limit symptoms of radiation proctitis. Methods and Materials: The first 18 patients received 1 g of intrarectal amifostine suspension placed 30-45 min before each radiation treatment. The following 12 patients received 2 g of amifostine. Total dose prescribed ranged from 66 to 76 Gy. All patients were treated with three-dimensional conformal radiation therapy. The suspension remained intrarectal during treatment and was expelled after treatment. For gastrointestinal symptoms, during treatment and follow-up, all patients had a Radiation Therapy Oncology Group (RTOG) grade recorded. Results: Median follow-up was 18 months (range, 6-24 months). With 2 g vs. 1 g amifostine, there was a nearly significant decrease in RTOG Grade 2 acute rectal toxicity. Seven weeks after the start of radiation therapy, the incidence of Grade 2 toxicity was 33% in the 1-g group (6/18) compared with 0% (0/12) in the 2-g group (p = 0.06). No Grade 3 toxicity or greater occurred in this study. Conclusion: This trial suggests greater rectal radioprotection from acute effects with 2 g vs. 1 g amifostine suspension. Further studies should be conducted in populations at higher risk for developing symptomatic acute and late proctitis

  13. Postmastectomy Hypofractionated and Accelerated Radiation Therapy With (and Without) Subcutaneous Amifostine Cytoprotection

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    Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis (Greece); Panteliadou, Marianthi; Abatzoglou, Ioannis M.; Sismanidou, Kyriaki [Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis (Greece); Sivridis, Efthimios; Giatromanolaki, Alexandra [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece)

    2013-01-01

    Purpose: Postmastectomy radiation therapy (PMRT) provides major local control and survival benefits. More aggressive radiation therapy schemes may, however, be necessary in specific subgroups, provided they are safely administered. We report the tolerance and efficacy of a highly accelerated and hypofractionated regimen (HypoARC). Methods and Materials: One hundred twelve high-risk patients who had undergone mastectomy received 10 consecutive fractions of 3.5 Gy in 12 days (thoracic wall and axillary/supraclavicular areas). Two consecutive additional fractions of 4 Gy were given to the surgical scar area (electrons 8-10 MeV) and 1 3.5-Gy fraction to the axilla (in cases with extensive nodal involvement). A minimum follow-up of 24 months (median, 44 months) was allowed before analysis. Of 112 patients, 21 (18.7%) refused to receive amifostine, the remaining receiving tolerance-based individualized doses (500-1000 mg/day subcutaneously). Results: By use of a dose individualization algorithm, 68.1%, 11%, and 18.7% of patients received 1000 mg, 750 mg, and 500 mg/day of amifostine. Patchy moist skin desquamation outside and inside the booster fields was noted in 14 of 112 (12.5%) and 26 of 112 (23.2%) patients, respectively. No case of acute pneumonitis was recorded. High amifostine dose offered a significant skin protection. Within a median follow-up time of 44 months, moderate subcutaneous edema outside and within the booster thoracic area was noted in 5 of 112 (4.4%) and 8 of 112 (7.1%) cases, respectively. Intense asymptomatic radiographic findings of in field lung fibrosis were noted in 4 of 112 (3.6%) patients. Amifostine showed a significant protection against lung and soft tissue fibrosis. A 97% projected 5-year local relapse free survival and 84% 5-year disease-specific survival were recorded. Lack of steroid receptor expression, simple human epidermal growth factor 2 positivity, or triple negative phenotype defined higher metastasis rates but had no effect on

  14. Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Trog, D.; Bank, P.; Wendt, T.G. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Radiation Oncology; Koscielny, S.; Beleites, E. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Ear Nose Throat Diseases

    1999-09-01

    Background: In patients with loco-regionally advanced head and neck cancer conventionally fractionated radiotherapy alone results in poor loco-regional control and survival rates. Treatment intensification by simultaneous administration of cytotoxic drugs produces higher acute morbidity. Therefore chemical radioprotection of normal tissues may be of clinical benefit. Patients and Methods: In a pilot study patients with advanced nonresectable head neck cancer treated with conventionally fractionated radical radiotherapy (60 to 66 Gy total doses) and concomitantly given 5-fluorouracil as protracted venous infusion, 250 mg/sqm/24 h over the entire treatment period were given amifostine 300 mg absolutely before each fraction. Acute treatment related mobidity was scored according to CTC classification and loco-regional control and survival rates were estimated. Comparison was made with a historical control group of identical chemoradiation but without amifostine application. Results: Chemoradiation induced oral mucositis was delayed and showed significant lower degrees at all 10 Gy increments (p<0.05) except 60 Gy and over (p>0.05). No significant toxicity was recorded with respect to blood pressure, serum calcium, potassium, hematologic parameters, emesis, nausea or body weight loss. Progression free survival and overall survival probability at 2 years were not statistically different in both cohorts. Conclusion: Amifostine given before each fraction of radiotherapy over 6 weeks has no cumulative toxicity, was well tolerated and may reduce treatment induced oral mucositis. No tumor protective effect was observed. (orig.) [German] Hintergrund: Bei Patienten mit lokoregionaer fortgeschrittenen Karzinomen im Kopf-Hals-Bereich fuehrt die alleinige konventionell fraktionierte Radiotherapie zu unuenstigen lokoregionaeren Tumorkontrollraten und Ueberlebensraten. Die Therapieintensivierung durch simultane Radiochemotherapie fuehrt zu gesteigerter Akutmorbiditaet. Die chemische

  15. Randomized phase III trial of postoperative radiochemotherapy ± amifostine in head and neck cancer. Is there evidence for radioprotection?

    International Nuclear Information System (INIS)

    Vacha, P.; Fehlauer, F.; Mahlmann, B.; Marx, M.; Richter, E.; Hinke, A.; Sommer, K.; Feyerabend, T.

    2003-01-01

    Purpose: Experimental and clincial data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. Patients and Methods: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to received RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m 2 carboplatin, day 1-5 week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the common toxicity criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. Results: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. Conclusions: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary. (orig.)

  16. Randomized phase III trial of postoperative radiochemotherapy {+-} amifostine in head and neck cancer. Is there evidence for radioprotection?

    Energy Technology Data Exchange (ETDEWEB)

    Vacha, P.; Fehlauer, F.; Mahlmann, B.; Marx, M.; Richter, E. [Dept. of Radiation Oncology and Nuclear Medicine, Univ. of Luebeck (Germany); Hinke, A. [WiSP Research Inst., Langenfeld (Germany); Sommer, K. [Dept. of Head and Neck Surgery, Univ. of Luebeck (Germany); Feyerabend, T. [Practice for Radiation Therapy Bonn-Rhein-Sieg, Bonn (Germany)

    2003-06-01

    Purpose: Experimental and clincial data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. Patients and Methods: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to received RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m{sup 2} carboplatin, day 1-5 week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the common toxicity criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. Results: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. Conclusions: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary. (orig.)

  17. Radio-modifying effects of amifostine analogues in whole body gamma irradiated mice

    International Nuclear Information System (INIS)

    Soni, Ravi; Arora, Aastha; Singh, Saurabh; Bhuria, Vikas; Sharma, Anjali; Bhatt, A.N.; Dwarakanath, B.S.; Pathak, Uma; Mathur, Shweta; Sandhir, Rajat

    2014-01-01

    Damage to hematopoietic and gastro-intestinal systems contribute mainly to acute effects (mortality) following exposures to moderate doses of ionizing radiation. The aminothiol, amifostine (WR2721, a FDA approved pro-drug) has been well established protector of normal tissues against radiation damage and chemo-therapeutic drugs induced toxicity. A number of amifostine analogues (DRDE-07, DRDE-30 and DRDE-35) have been recently synthesized that afford protection against Sulfur Mustard (SM) when administered orally. Since, the mechanisms underlying toxicity by SM share a great deal with ionizing radiation and certain anti-cancer drugs, we investigated the potential of DRDE analogues in reducing the acute effects of radiation in whole body irradiated mice. Animal survival, body weight, changes in haematological parameters and CFU-S as well as morphology of GI was studied. DRDE analogues significantly enhanced the animal survival and reduced the radiation sickness (loss of weight) in a dose dependent manner when administered 30 min. before irradiation; optimal doses were 125 mg/kg body weight for DRDE-07; 220 mg/kg for DRDE-30 and 200 mg/kg for DRDE-35. All three analogues were orally effective unlike amifostine, albeit to different extents. The order of radio-protective efficacy in C57BL/6 mice when administered orally was DRDE-35 (60%) > DRDE-07 (50%) > DRDE-30 (40%), while it was DRDE-07 (58%) > DRDE-30 (44%) > DRDE-35 (40%) following intra-peritoneal administration. These analogues enhanced the recovery from radiation-induced hematopoietic damage (peripheral blood counts and improvement in endogenous spleen colony forming units) and gastrointestinal injury (improved structural integrity of GI, increase in villi height, regenerating crypts and mitotic figures) that correlated with the increase in survival. There were no survivors in the radiation group after 35 days of exposure and the values for the analyzed parameters were comparable to the control group. These

  18. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

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    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  19. Does amifostine have radioprotective effects on salivary glands in high-dose radioactive iodine-treated differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Chao; Wang, Guoming; Zuo, Shuyao [Qingdao University, Department of Nuclear Medicine, Affiliated Hospital, Medical College, Qingdao, Shandong Province (China); Xie, Jiawei [Qingdao University, Medical College, Qingdao (China); Jiang, Zhongxin [Qingdao University, Affiliated Hospital, Medical College, Qingdao (China)

    2010-09-15

    To assess the effects of amifostine on salivary glands in radioactive iodine-treated differentiated thyroid cancer. We searched the MEDLINE, EMBASE and the Cochrane Library for randomized controlled clinical trials which compared the effects of amifostine with those of placebo or acid-stimulating agents. Two randomized controlled clinical trials with a total of 130 patients were included. Both studies had a low risk of bias. There were no statistically significant differences between the effects of amifostine and acid-stimulating agents on the incidence of xerostomia (RR 0.24, 95% CI 0.01 to 9.52), the decrease of scintigraphically measured uptake of {sup 99m}Tc by the parotid (RR 0.30, 95% CI -2.28 to 2.88) or submandibular glands (RR 1.90, 95% CI -1.46 to 5.26) at 12 months, or the reduction in blood pressure (RR 5.00, 95% CI 0.25 to 99.16). Neither of the included trials investigated death from any cause, morbidity, health-related quality of life or costs. The results of two randomized controlled clinical trials suggest that amifostine has no significant radioprotective effects on salivary glands in radioactive iodine treatment of differentiated thyroid cancer. The use of acid-stimulating agents to increase salivation should remain the first choice during radioactive iodine treatment of differentiated thyroid cancer. Patients should also be well informed of the importance of hydration and acid stimulation. (orig.)

  20. Assessment of the radioprotective effects of amifostine and melatonin on human lymphocytes irradiated with gamma-rays in vitro

    International Nuclear Information System (INIS)

    Kopjar, N.; Miocic, S.; Ramic, S.; Milic, M.; Viculin, T.

    2005-01-01

    Radioprotective effects of amifostine and melatonin on human peripheral blood irradiated with g-rays were investigated using the micronucleus (MN) assay and the analysis of sister chromatid exchanges (SCE). Duplicate blood samples were pre-treated with amifostine (7.7 mM), melatonin (2 mM) and their combination for 30 minutes. Negative controls were also included. After treatment with radioprotectors, one blood sample from each experimental group was exposed to g-rays from a 6 0C o source. The radiation dose absorbed was 2 Gy. Pre-treated irradiated blood samples showed a decrease in the total number of MN and in the number of cells with more than one MN. Moreover, they also showed significantly lower mean SCE values. Our results indicate that amifostine, melatonin and their combination in vitro have radioprotective effects on g-irradiated human peripheral blood lymphocytes, with no significant genotoxicity. Therefore, it may be reasonable to use them in combination, adjusting the doses of amifostine to achieve the best radioprotective effect with as few side effects as possible. Before employment, this combination should be extensively tested in vitro and in vivo, using the same and other biomarkers for different radiation dose and concentration ranges of both radioprotectors.(author)

  1. Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

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    Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

    2016-09-15

    This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

  2. Amifostine (WR-2721, a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

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    De Souza C.A.

    2000-01-01

    Full Text Available Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY (7 g/m2, used to mobilize peripheral blood progenitor cells (PBPC and to reduce tumor burden. We enrolled 29 patients, 22 (75.9% affected by aggressive and 7 (24.1% by indolent non-Hodgkin's lymphoma (NHL, who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04. None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively. Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

  3. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

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    Vuslat Yurut-Caloglu

    2015-01-01

    Full Text Available Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7; irradiation alone RT: radiation therapy (RT, n = 8; amifostine plus irradiation (AMI + RT, n = 8; LC plus irradiation (LC + RT, n = 8; LC and sham irradiation (LC, n = 7; and amifostine and sham irradiation (AMI, n = 7. The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg and amifostine (200 mg/kg was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA and advanced oxidation protein product (AOPP were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P 0.05. The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P 0.005. The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005. Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

  4. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    International Nuclear Information System (INIS)

    Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki; Botaitis, Sotirios; Torvinen, Sira; Simopoulos, Constantinos; Kortsaris, Alexandros; Sivridis, Efthimios; Koukourakis, Michael I.

    2011-01-01

    Research highlights: → We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. → Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. → The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. → Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body γ-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 m

  5. Efficacy and Safety of Subcutaneous Amifostine in Minimizing Radiation-Induced Toxicities in Patients Receiving Combined-Modality Treatment for Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Law, Amy; Kennedy, Thomas; Pellitteri, Phillip; Wood, Craig; Christie, Douglas; Yumen, Omar

    2007-01-01

    Purpose: To report long-term data from a prospective trial of subcutaneous (s.c.) amifostine in patients who received chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: Patients ≥18 years of age with previously untreated Stage III/IV SCCHN received fractionated radiotherapy, 1.8-2.0 Gy/day, 5 days per week, to a total dose of 70-72 Gy, plus weekly paclitaxel (40 mg/m 2 ) and carboplatin (100 mg/m 2 ) administered intravenously (i.v.) for 6 weeks. All patients received 500 mg s.c. amifostine 30-60 min before radiotherapy with antihistamine and antiemetic prophylaxis. Results: Twenty patients were evaluable (median age, 55 years). The incidence of Grade 2 xerostomia was 42% and 29% at 12 and 18 months, respectively; there were no reports of Grade ≥3 xerostomia. Grade ≥3 mucositis occurred in 30% of patients, with median time to resolution of 12.5 weeks (range, 5-17 weeks). Survival estimates at 1 and 2 years were 95% and 71%, respectively. All patients experienced Grade 2 weight loss; 7 patients (35%) experienced Grade ≤2 nausea/vomiting. There were no reports of Grade ≥3 amifostine-related adverse events. Conclusions: Subcutaneous amifostine was well tolerated by patients receiving chemoradiotherapy for SCCHN, with lower rates of nausea/vomiting than reported in trials with i.v. amifostine. Xerostomia and mucositis rates were similar to those reported in trials with i.v. amifostine

  6. [Protective effects of amifostine on hematopoietic stem/progenitor cells against chemotherapeutic damage].

    Science.gov (United States)

    Chen, Bao-An; Li, Cui-Ping; Zhou, Min; Gao, Chong; Ding, Jia-Hua

    2004-12-01

    The aim was to study the protective effects of amifostine (AMF) on normal hematopoietic stem/progenitor cells against the chemotherapeutic damage from etoposide (VP-16). The cord blood mononuclear cells (CBMNC), fresh and frozen peripheral blood stem cells (PBSC), and HL-60 cells were divided into AMF, AMF + VP-16, VP-16 and control groups, each group cell viability was determined by using trypan blue exclusion test, the CFU-GM culture was used to count cells, the apoptosis was detected by flow cytometry. The results showed that in CBMNC, fresh and frozen PBSC samples, cell viability and the number of CFU-GM in AMF + VP-16 group were all significantly higher than those in VP-16 group (P GFU-GM life in AMF + VP-16 group was also longer than that of latter, in CBMNC samples, the number of CFU-GM in AMF groups was higher than that in control group, but there was no statistical significance between the two groups (P > 0.05), in HL-60 cell apoptotic rate in AMF + VP-16 group was little higher than that in VP-16 group, but no statistical significance between these two groups (P > 0.05). It is concluded that AMF can significantly protect normal hematopoietic stem/progenitor cells against the damage from VP-16. Moreover, AMF does not affect cytotoxity of VP-16 on HL-60 cells, and can not stimulate the growth and differentiation of cord hematopoietic stem/progenitor cells directly.

  7. Open label multicenter trial of subcutaneous amifostine (Ethyol) in the prevention of radiation induced esophagitis and pneumonitis in patients with measurable, unresectable non-small cell lung cancer.

    Science.gov (United States)

    Mehta, Vivek

    2004-12-01

    While concurrent delivery of chemotherapy and radiotherapy (RT) has a synergistic effect on tumor control and improves the median and overall survival in patients with locally advanced non-small cell lung cancer, appreciable acute and late morbidity occur to the esophagus and the lung during treatment (ie, acute radiation esophagitis, pulmonary toxicity). Emerging evidence suggests that the volume of normal lung exposed to certain threshold doses of RT might predict for the incidence of pneumonitis. Clinical data also indicate that amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD), an organic thiophosphate, acts as a selective cytoprotective agent for normal tissues against the toxicities of chemotherapy and RT. Moreover, preclinical and clinical data suggest that subcutaneous administration of amifostine may be better tolerated with similar efficacy to that of the intravenous route. We are conducting an open-label trial that is accruing patients with locally advanced non-small cell lung cancer, who will receive concurrent chemoradiotherapy (cisplatin/etoposide or carboplatin/paclitaxel plus RT delivered using 3-dimensional conformal radiotherapy treatment planning) and amifostine 500 mg before RT. Incidence and severity of acute radiation esophagitis, acute radiation pneumonitis, chronic radiation pneumonitis, and changes in pulmonary function will be recorded, as will elements of the RT treatment planning (eg, dose volume histogram data for the lung and esophagus). Pre- and post-therapy pulmonary function is a primary endpoint, and others include general safety assessments of subcutaneous amifostine administration.

  8. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    International Nuclear Information System (INIS)

    Wasserman, Todd H.; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-01-01

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m 2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade ≥2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival

  9. Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats

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    Dragojević-Simić Viktorija

    2013-01-01

    Full Text Available Background/Aim. Amifostine (AMI is a broad-spectrum cytoprotector which protects against variety of radio- and chemotherapy-related toxicities without decreasing their antitumor action. The aim of the study was to investigate the potential protective effects of AMI against acute cardiotoxic effects of doxorubicin (DOX in male Wistar rats. Methods. AMI (300 mg/kg ip was given 30 min before DOX (6 mg/kg and 10mg/kg b.w., iv. The evaluation of DOXinduced cardiotoxic effects, as well as cardioprotective efficacy of AMI was performed 48 h after their administration by determining serum activities of enzymes known to be markers of cardiac damage (creatine kinase - CK, aspartate aminotransferase - AST, lactate dehydrogenase - LDH, and its isoenzyme α-hydroxybutirate dehydrogenase - α- HBDH, as well as the histopathological and ultrastructural analysis of the heart tissue. Results. AMI successfully prevented a significant increase in serum activity of CK, AST, LDH and α-HBDH in animals treated with DOX in the dose of 6 mg/kg (121.14 ± 18.37 vs 167.70 ± 44.24; 771.42 ± 161.99 vs 1057.00 ± 300.00; 3230.00 ± 1031.73 vs 4243.10 ± 904.06; 202.57 ± 42.46 vs 294.90 ± 80.20 UI/l, respectively, and ameliorated DOX-induced structural damage of the rat myocardium. Pretreatment with AMI in rats given 10 mg/kg DOX reduced the cardiac damage score (CDS from 2.62 ± 0.51 to 1.62 ± 0.51, i.e. to the CDS value obtained with the lower dose of DOX (6 mg/kg. The ultrastructural analysis of the rat myocardium showed that AMI successfully protected the sarcolemma of cardiomyocytes and reduced mitochondria damage induced by DOX given in the dose of 6 mg/kg. Besides, capillaries were less morphologically changed and apoptosis of endothelial cells was extremely rare in AMI-protected animals. AMI itself did not cause any prominent changes in the examined parameters in comparison with the control rats. Conclusion. AMI provided a significant protection against DOX

  10. Radioprotection of salivary glands by amifostine in high-dose radioiodine treatment. Results of a double-blinded, placebo-controlled study in patients with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bohuslavizki, K.H.; Klutmann, S.; Kroeger, S.; Buchert, R.; Bleckmann, C.; Mester, J.; Clausen, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. Nuklearmedizin; Brenner, W.; Henze, E. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin

    1999-11-01

    Background and purpose: Parenchymal impairment of salivary glands following high-dose radioiodine treatment is a well-known side effect in general caused by free radicals. Therefore, the radioprotective effect of the radical scavenger amifostine was evaluated prospectively in patients receiving high-dose radioiodine treatment. Patients and methods: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed in 50 patients with differentiated thyroid cancer prior to and 3 months after high-dose radioiodine treatment with either 3 GBq {sup 131}I (n=21) or 6 BGq {sup 131}I (n=29) in a double-blinded, placebo-controlled study. Twenty-five patients treated with 500 mg/m{sup 2} amifostine intravenously prior to high-dose radioiodine treatment were compared to 25 control patients receiving physiological saline solution. Xerostomia was graded according to WHO-criteria. Results: In 25 control patients high-dose radioiodine treatment significantly (p<0.001) reduced parenchymal function of parotid and submandibular glands by 40.2{+-}14.1% and 39.9{+-}15.3%, respectively. Nine out of these 25 patients developed Grade I and 2 Grade II xerostomia. In contrast, in 25 amifostine-treated patients there was no significant (p=0.691) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. Conclusion: Parenchymal damage of salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine which may improve quality of life of patients with differentiated thyroid cancer. (orig.) [German] Hintergrund und Ziel: Eine Schaedigung der Speicheldruesen mit konsekutiver Xerostomie ist eine bekannte, durch freie Radikale verursachte Nebenwirkung der ablativen Radioiodtherapie bei Patienten mit differenziertem Schilddruesenkarzinom. Daher wurde der Effekt des Radikalfaengers Amifostin bei ablativer Radioiodtherapie geprueft. Patienten und Methoden: Es wurden insgesamt 50

  11. Zytoprotektion mit Amifostin (Ethyol®) in der Chemotherapie: Meta-Analyse zum pharmakokinetischen Interaktionspotential mit Zytostatika.

    Science.gov (United States)

    Czejka, Martin; Schüller, Johannes; Kletzl, Heidemarie

    2017-08-25

    The cytoprotective agent amifostine (AMI) is capable to protect healthy cells (contrary to tumor cells) due to higher activity of alkaline phosphatase at the membrane site of normal cells. In seven clinical trials the influence of AMI on the pharmacokinetics of different cytostatics was investigated. Preadministration of AMI increased Cmax of doxorubicin (+ 44 %, p < 0.06), epirubicin (+ 31 %, P < 0.08), mitomycin C (+ 41 %, p < 0.01) and docetaxel (+ 31 % and + 17 %, not significant). In contrary, the peak concentration of pirarubicin , the tetrahydropyranyl-prodrug of doxorubicin was decreased (- 50 %, P < 0.03), leading to an equal higher concentrationof doxorubicin in the blood . In accordance to the peak concentrations, the AUC'ast was increased by chemoprotection: doxorubicin + 53 % (p < 0.01) and epirubicin + 23 % (not significant), docetaxel + 25 % and + 31 % (not significant). AUC'ast of mitomycin C and paclitaxel seemed to be unaffected by preadministered AMI. A particular inhibition of the protein binding by AMI has been identified as one reason for higher serum concentrations of anthracycline drugs. After cytoprotection, a possible increase of the cytostatic's Serum concentrations should be taken into account for optimal dosage schedules.

  12. Reduction of treatment breaks and radiation-induced esophagitis and pneumonitis using amifostine in unresectable non-small cell lung cancer patients receiving definitive concurrent chemotherapy and radiation therapy: a prospective community-based clinical trial.

    Science.gov (United States)

    Wynn, Raymond B; Mehta, Vivek

    2005-04-01

    Concurrent chemotherapy with daily thoracic radiation therapy is a common regimen used in patients with non-small cell lung cancer resulting in excellent response rates but with appreciable morbidity. Radiation-induced toxicities may increase the number of treatment breaks and then may limit the use of this aggressive treatment approach for some patients. We are conducting an open-label, multicenter trial determining the incidence of radiation treatment breaks and severity of treatment-related toxicities with the concurrent use of a cytoprotective agent. Approximately 15 to 20 sites in the United States will participate with a total of 200 patients. Patients will receive one of two chemotherapy regimens and daily radiation (1.8 to 2.0 Gy daily; total dose, 60 to 70 Gy) and amifostine 500 mg subcutaneously or intravenous push daily over a 6- to 7-week period. Patients will receive amifostine (Ethyol; MedImmune Inc, Gaithersburg, MD) 500 mg daily. The route of amifostine administration chosen at the time of patient registration must be adhered to throughout the study. In addition, all patients may receive consolidation chemotherapy consisting of intravenous docetaxel 75 mg/m 2 once every 3 weeks for three courses, starting more than 30 but less than 60 days after the last dose of amifostine or thoracic radiation therapy, whichever is the last therapy discontinued. The objectives of this study are to determine the incidence of radiation treatment breaks and evaluate acute radiation esophagitis, acute radiation pneumonitis, chronic radiation pneumonitis, and pulmonary function in patients with measurable, medically inoperable non-small cell lung cancer stage II, unresectable stage IIIA, or IIIB disease receiving combined modality therapy and amifostine.

  13. Analysis of the cytoprotective effect of amifostine on the irradiated inner ear of guinea pigs: an experimental study Análise do efeito citoprotetor da amifostina na orelha interna irradiada de cobaias: estudo experimental

    Directory of Open Access Journals (Sweden)

    Ricardo Miranda Lessa

    2009-10-01

    Full Text Available Radiation can cause damage to the inner ear, from a simple hearing loss all the way to profound deafness. Amifostine is a cytoprotective substance extensively used during radio-chemotherapy for malignant tumors. AIM: the objective of the present investigation was to establish the antioxidant and radioprotective effects of amifostine on the organ of Corti of albino guinea pigs irradiated in the head and neck region. MATERIALS AND METHODS: An experimental study conducted on four groups of guinea pigs were used; One group received only amifostine, one group was submitted to a single dose of 350 cGy and the other two were similarly irradiated but received amifostine doses of 100 or 200 mg/kg. All animals were slaughtered 30 days after the experiment, their bullae were removed and the damaged outer hair cells were counted. RESULT: The extent of injury was lower in the outer hair cells of the two groups treated with amifostine compared to the group that was only irradiated. There was no difference between the group treated with 100 and 200 mg/kg of amifostine. The group that received only amifostine had no cochlear damage. CONCLUSION: Amifostine is an effective cytoprotective substance in the Organ of Corti of irradiated guinea pigs.A radiação pode causar lesão na orelha interna podendo provocar surdez sensório-neural e inclusive levar à anacusia. A amifostina é uma substância citoprotetora seletiva de tecidos sadios, amplamente utilizada durante a radio e quimioterapia de tumores malignos. OBJETIVO: O objetivo deste estudo experimental foi verificar se existe efeito antioxidante e radioprotetor da amifostina no órgão de Corti de cobaias albinas irradiadas em região de cabeça e pescoço. MATERIAL E MÉTODO: O estudo realizado envolveu quatro grupos de animais: um grupo foi submetido à irradiação em dose única de 350cGy. Dois grupos receberam a mesma dose de radiação, porém receberam doses de 100 e 200mg/kg de amifostina, 30 minutos

  14. Development and Validation of an HPLC Method for Determination of Amifostine and/or Its Metabolite (WR-1065) In Human Plasma Using OPA Derivatization and UV Detection.

    Science.gov (United States)

    Samiei, Nasim; Foroutan, Seyed Mohsen; Shafaati, Alireza; Zarghi, Afshin

    2015-01-01

    A rapid, sensitive and reproducible HPLC method was developed and validated for the analysis of amifostine (AMF) and/or its metabolite, WR-1065 in human plasma. The method involves the alkylation of free sulfydryl group with iodoacetic acid followed by derivatization of the drug and its metabolite with o-phthaldialdehyde (OPA) and UVdetection at 340 nm. The derivatized AMF and WR-1065 were eluted in less than 11 min, and in the case of the metabolite with no interferences from the endogenous plasma peaks. Cystein was used as the internal standard. Analysis was carried out on a Eurosphere Performance (RP-18e, 100 × 4.6 mm) analytical column. The mobile phase was a mixture of methanol and phosphate buffer 0.03 M pH = 2.7 at a ratio of 40: 60v/v, respectively, with a flow rate of 1.5 mLmin(-1). Limit of detection was 0.5 µgmL(-1). The method involved a simple extraction procedure for AMF and/or its metabolite and analytical recovery was 90 ± 0.9%.The calibration curve was linear over the concentration range of 1-200 µgmL(-1). The coefficients of variation for intra-day and inter-day assays were less than 10%.

  15. Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Garces, Yolanda I.; Okuno, Scott H.; Schild, Steven E.; Mandrekar, Sumithra J.; Bot, Brian M.; Martens, John M.; Wender, Donald B.; Soori, Gamini S.; Moore, Dennis F.; Kozelsky, Timothy F.; Jett, James R.

    2007-01-01

    Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m 2 ) Days 1 to 5 and paclitaxel (175 mg/m 2 ) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard 'cohorts of 3' design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m 2 ) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade ≥4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade ≥3 dyspnea, or Grade ≥2 pneumonitis. Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade ≥3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine

  16. Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Falk, Martin; Komůrková, Denisa; Falková, Iva; Bačíková, Alena; Klejdus, B.; Pagáčová, Eva; Štefančíková, Lenka; Weiterová, Lenka; Angelis, Karel; Kozubek, Stanislav; Dušek, L.; Galbavy, S.

    2016-01-01

    Roč. 59, č. 7 (2016), s. 3003-3017 ISSN 0022-2623 R&D Projects: GA ČR GBP302/12/G157; GA ČR(CZ) GA16-12454S Institutional support: RVO:68081707 Keywords : alternative splicing variant * order chromatin-structure Subject RIV: BO - Biophysics Impact factor: 6.259, year: 2016

  17. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

    DEFF Research Database (Denmark)

    Jensen, S.B.; Pedersen, A.M.L.; Vissink, A.

    2010-01-01

    , amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment....... Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant...... formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia...

  18. Mutagenicity and antimutagenicity studies of DRDE-07 and its analogs against sulfur mustard in the in vitro Ames Salmonella/microsome assay.

    Science.gov (United States)

    Vijayan, Vinod; Pathak, Uma; Meshram, Ghansham Pundilikji

    2014-10-01

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM), a chemical warfare agent, is classified as a class I human carcinogen by IARC. No effective antidote against this agent is available. The synthetic aminothiol, amifostine, earlier known as WR-2721, has been extensively used as a chemical radioprotector for normal tissues in cancer radiotherapy and chemotherapy. SM is a radiomimetic agent; this prompted us to evaluate the protective efficacy of amifostine and three of its analogs, DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulphide], DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide] and DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide], against sulfur mustard-induced mutagenicity in the Ames Salmonella/microsome assay. The antidotes were also evaluated for possible mutagenic activity. DRDE-07 was mutagenic in strain TA104 in the absence of S9; DRDE-30 was mutagenic in strain TA100; amifostine and DRDE-35 did not show mutagenic activity in any of the five tester strains used. SM is mutagenic in strains TA97a and TA102, with or without S9 activation. In the antimutagenicity studies, DRDE-07 and DRDE-35 showed promising antimutagenic activity against SM in the absence of S9, in comparison to amifostine. DRDE-07 and DRDE-35 are promising protective agents against SM-induced mutagenicity. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Induction of apoptosis and cell proliferation inhibition by paclitaxel in ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-02-18

    Feb 18, 2009 ... also used molecular biology methods and morphological imaging ... C47H51NO14 and its molecular weight is 853.9 (Mastropaolo et al.,. 1995). ..... Biologia. 60: 325-330. Arican Özcan G (2005b). Cytoprotective effects of amifostine and cysteamine on cultured normal and tumor cells treated with paclitaxel.

  20. Differential effect triggered by a heparan mimetic of the RGTA family preventing oral mucositis without tumor protection.

    Science.gov (United States)

    Mangoni, Monica; Yue, Xiaoli; Morin, Christophe; Violot, Dominique; Frascogna, Valerie; Tao, Yungan; Opolon, Paule; Castaing, Marine; Auperin, Anne; Biti, Giampaolo; Barritault, Denis; Vozenin-Brotons, Marie-Catherine; Deutsch, Eric; Bourhis, Jean

    2009-07-15

    Oral mucositis is a common side effect induced by radio/chemotherapy in patients with head and neck cancer. Although it dramatically impairs patient quality of life, no efficient and safe therapeutic solution is available today. Therefore, we investigated the protective efficacy of a new heparan mimetic biopolymer, RGTA-OTR4131, used alone or in combination with amifostine, for oral mucositis and simultaneously evaluated its effect on tumor growth in vitro and in vivo. A single dose of 16.5 Gy was selectively delivered to the snout of mice, and the effects of OTR4131 or amifostine-OTR4131 were analyzed by macroscopic scoring and histology. The effect of OTR4131 administration on tumor growth was then investigated in vitro and in xenograft models using two cell lines (HEP-2 and HT-29). Amifostine and OTR4131 significantly decreased the severity and duration of lip mucosal reactions. However, amifostine has to be administered before irradiation, whereas the most impressive protection was obtained when OTR4131 was injected 24 h after irradiation. In addition, OTR4131 was well tolerated, and the combination of amifostine and OTR4131 further enhanced mucosal protection. At the tumor level, OTR4131 did not modify HEP-2 cell line clonogenic survival in vitro or protect xenografted tumor cells from radiotherapy. Of interest, high doses of OTR4131 significantly decreased clonogenic survival of HT-29 cells. RGTAs-OTR4131 is a well-tolerated, natural agent that effectively reduces radio-induced mucositis without affecting tumor sensitivity to irradiation. This suggests a possible transfer into the clinic for patients' benefit.

  1. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

    DEFF Research Database (Denmark)

    Jensen, Siri Beier; Pedersen, Anne Marie Lynge; Vissink, Arjan

    2010-01-01

    /PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome......, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment....... Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant...

  2. Department of Clinical Investigation, Annual Research Progress Report, Fiscal Year 2007 (Madigan Army Medical Center)

    Science.gov (United States)

    2007-09-30

    McNutt PM, DeHart MJ, Matej LA. Characterization of the 16S-23S internal transcribed spacer among 34 hight plants : Suitability for interspecific...plastid transformation. Plant Cell Reports 47(60): p. 47-60, 2007. Merrill NL, Burge R. Effects of Three Mydriatic Drug Regimens on Pupil Size in...Wills BK, Aks S, Maloney GE, Rhee J, Brand R, Sekosan M. The effect of amifostine, a cytoprotective agent, on paraquat toxicity in mice. Journal of

  3. Novel use of zebrafish as a vertebrate model to screen radiation protectors and sensitizers

    International Nuclear Information System (INIS)

    Purpose: Zebrafish (Danio rerio) embryos provide a unique vertebrate model to screen therapeutic agents easily and rapidly because of their relatively close genetic relationship to humans, ready abundance and accessibility, short embryonal development, and optical clarity. To validate zebrafish embryos as a screen for radiation modifiers, we evaluated the effects of ionizing radiation in combination with a known radioprotector (free radical scavenger Amifostine) or radiosensitizing agent (tyrosine kinase inhibitor AG1478). Methods and materials: Viable zebrafish embryos were exposed to 0-10 Gy single-fraction 250 kVp X-rays with or without either Amifostine (0-4 mM) or AG1478 (0-10 μM) at defined developmental stages from 1-24 h postfertilization (hpf). Embryos were examined for morphologic abnormalities and viability until 144 hpf. Results: Radiation alone produced a time- and dose-dependent perturbation of normal embryonic development and survival with maximal sensitivity at doses ≥4 Gy delivered before 4 hpf. Amifostine markedly attenuated this effect, whereas AG1478 enhanced teratogenicity and lethality, particularly at therapeutically relevant (2-6 Gy) radiation doses. Conclusions: Collectively, these data validate the use of zebrafish as a vertebrate model to assess the effect of radiation alone or with radiation response modulators. Zebrafish embryos may thus provide a rapid, facile system to screen novel agents ultimately intended for human use in the context of therapeutic or accidental radiation exposure

  4. The progress in treatment of severe hematopoietic and intestinal form of acute radiation syndrome

    International Nuclear Information System (INIS)

    Hu Kaixun; Ai Huisheng

    2006-01-01

    The acute radiation syndrome (ARS) is hard to be overcome as the hot medical problem. This article presents the recent advances in the treatment: (1) The amifostin (WR-2721) be mechanism and earlier periods of the cell protection to apply may interrupt organize harm. (2) New directions for therapy are stressed, using cytokines to enhance recovery of hematopoiesis and immune reconstitution. (3) The article presents guidelines for the use of hematopoietic stem cell transplantation and the mesenchymal stem cells (MSCs) have the importance treatment meaning to the ARS. (4) Indications of preemptive therapy of fungal infection in patients are described. (authors)

  5. Evaluation of the radioprotective effect of Turkish propolis on foreskin fibroblast cells.

    Science.gov (United States)

    Yalcin, Can Ozgur; Aliyazicioglu, Yuksel; Demir, Selim; Turan, Ibrahim; Bahat, Zumrut; Misir, Sema; Deger, Orhan

    2016-01-01

    Propolis is a resinous bee product, rich of polyphenolic compounds and flavonoids. It is known that in different geographic zones its chemical composition varies due to the different plant sources. Many biological properties including antimicrobial, antioxidative, anti-inflammatory, antitumoral, antigenotoxic, antimutagenic, cytostatic activities have been ascribed to propolis. These biological effects are predominantly attributed to its content of polyphenols. In this study, we aimed to evaluate the radioprotective effect of ethanolic extract of Turkish propolis. (EETP) against γ-ray-induced DNA damage on fibroblast cells using comet assay for the first time. Fibroblast cells were pretreated 15 and 30 min with concentrations of 100, 200 and 300 μg/mL EETP then they were exposed to 3 Gy γ-rays. Amifostine (synthetic aminothiol compound) was used as a positive control. The results showed a significant decrease in γ-ray-induced DNA damage on cells treated with EETP and amifostine when compared to only irradiated cells. (P < 001). It was concluded that EETP prevent γ-ray-induced DNA damage in fibroblast cells and might have radioprotective activity.

  6. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact.

    Science.gov (United States)

    Jensen, S B; Pedersen, A M L; Vissink, A; Andersen, E; Brown, C G; Davies, A N; Dutilh, J; Fulton, J S; Jankovic, L; Lopes, N N F; Mello, A L S; Muniz, L V; Murdoch-Kinch, C A; Nair, R G; Napeñas, J J; Nogueira-Rodrigues, A; Saunders, D; Stirling, B; von Bültzingslöwen, I; Weikel, D S; Elting, L S; Spijkervet, F K L; Brennan, M T

    2010-08-01

    This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

  7. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  8. Evaluation, prevention and management of radiotherapy-induced xerostomia in head and neck cancer patients.

    Science.gov (United States)

    de Castro, Gilberto; Federico, Miriam Hatsue Honda

    2006-05-01

    As part of the multidisciplinary approach to head and neck cancer patients, radiation therapy plays an essential role, improving locoregional control. Radiation therapy-induced xerostomia is a late side-effect that increases the risk for developing dental caries and compromises oral mucosal integrity, resulting in oral pain, loss of taste, difficulties with swallowing and chewing, sleep disorders and worse quality of life. This review focuses on evaluation, prevention and management of radiation therapy-induced xerostomia. In terms of xerostomia prevention, some clinical trials evaluating amifostine and intensity-modulated radiation therapy have shown positive results. Pilocarpine is a useful agent as a treatment of radiation-induced xerostomia in head and neck cancer patients. Despite some advances in radiation therapy-induced xerostomia prevention, its treatment is an area in which advances are urgently needed.

  9. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

    DEFF Research Database (Denmark)

    Jensen, Siri Beier; Pedersen, Anne Marie Lynge; Vissink, Arjan

    2010-01-01

    This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE/PubMed and E......This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE......, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment...... formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia...

  10. High glucose inhibits the aspirin-induced activation of the nitric oxide/cGMP/cGMP-dependent protein kinase pathway and does not affect the aspirin-induced inhibition of thromboxane synthesis in human platelets.

    Science.gov (United States)

    Russo, Isabella; Viretto, Michela; Barale, Cristina; Mattiello, Luigi; Doronzo, Gabriella; Pagliarino, Andrea; Cavalot, Franco; Trovati, Mariella; Anfossi, Giovanni

    2012-11-01

    Since hyperglycemia is involved in the "aspirin resistance" occurring in diabetes, we aimed at evaluating whether high glucose interferes with the aspirin-induced inhibition of thromboxane synthesis and/or activation of the nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (PKG) pathway in platelets. For this purpose, in platelets from 60 healthy volunteers incubated for 60 min with 5-25 mmol/L d-glucose or iso-osmolar mannitol, we evaluated the influence of a 30-min incubation with lysine acetylsalicylate (L-ASA; 1-300 μmol/L) on 1) platelet function under shear stress; 2) aggregation induced by sodium arachidonate or ADP; 3) agonist-induced thromboxane production; and 4) NO production, cGMP synthesis, and PKG-induced vasodilator-stimulated phosphoprotein phosphorylation. Experiments were repeated in the presence of the antioxidant agent amifostine. We observed that platelet exposure to 25 mmol/L d-glucose, but not to iso-osmolar mannitol, 1) reduced the ability of L-ASA to inhibit platelet responses to agonists; 2) did not modify the L-ASA-induced inhibition of thromboxane synthesis; and 3) prevented the L-ASA-induced activation of the NO/cGMP/PKG pathway. Preincubation with amifostine reversed the high-glucose effects. Thus, high glucose acutely reduces the antiaggregating effect of aspirin, does not modify the aspirin-induced inhibition of thromboxane synthesis, and inhibits the aspirin-induced activation of the NO/cGMP/PKG pathway. These results identify a mechanism by which high glucose interferes with the aspirin action.

  11. Radiation 2006. In association with the Polymer Division, Royal Australian Chemical Institute. Incorporating the 21st AINSE Radiation Chemistry Conference and the 18th Radiation Biology Conference, conference handbook

    International Nuclear Information System (INIS)

    Martin, R. F.; Smith, A.; Lobachevsky, P.; Karagiannis, T; Leung, B.; Andrau, L.; White, J.

    2006-01-01

    Full text: Methylproamine is the current lead compound of a new class of DNA-binding radioprotectors being developed in the Research Laboratories at the Peter MacCallum Cancer Centre in Melbourne. The salient features of methylproamine are its radioprotective potency and the generic nature of the apparent radioprotective mechanism. Like the 'classic' aminothiol radioprotectors exemplified by amifostine, methylproamine suppresses the initial radiochemical damage induced in DNA by ionising radiation. However, survival curve studies with cultured cells have demonstrated that methylproamine is 100-fold more potent than WR1065, the active metabolite of amifostine. The radioprotective mechanism seems to involve reduction by the DNA-bound drug of transient radiation-induced oxidising species on DNA. This mechanism implies some electron transfer along DNA, from the DNA-bound drug to the oxidising species. In vivo radioprotection of mouse lung, GI tract and bone marrow has been demonstrated following systemic administration of methylproamine to mice. The commercial potential of radioprotectors resides in two distinct arenas. Until recently, most of our efforts have focused on the use of methylproamine to protect normal tissues in cancer radiotherapy patients, but a quite different opportunity arises from the imperative to develop countermeasures to the threat of radiation terrorism. Our prospects in both arenas have been lifted by the results of synthesis and screening of a pilot library of ∼50 methylproamine analogues, promising the emergence of new lead drugs. In particular, although methylproamine is a potent radioprotector, at higher concentrations it becomes cytotoxic, but one member of the pilot library shows a wider efficacy 'window'. We plan to continue this lead optimisation process by synthesis and screening of a much larger library of analogues, and we are seeking the support of a commercial partner

  12. Neonatal irradiation: neurotoxicity and modulation of pharmacological response

    International Nuclear Information System (INIS)

    Zieher, Luis M.; Guelman, Laura R.

    2001-01-01

    Neuronal loss may be responsible of many acute and chronic diseases. For this reason, is very important to understand the mechanisms that contribute to neuronal cell death in order to develop pharmacological strategies for the treatment of these disorders. Developing CNS is very sensitive to ionizing radiations. In particular, irradiation of immature cerebellum induce motor (impaired gait), morphological (disarrangement of cytoarchitecture) and biochemical (increase in noradrenaline levels) alterations, mainly related to cerebellar granule cell death induced by reactive oxygen species (ROS) generated after radiation exposure. Cellular changes triggered by ROS include increased intracellular Ca 2+ levels, activation of NMDA glutamatergic receptors and apoptosis. With an excitatory neurotransmitter as glutamate and a multifacetic ion as calcium, their regulation in synapses and cytoplasm, respectively, is very vulnerable. Moreover, the highly aerobic condition of neuronal metabolism determines that an oxidative injury lead to ROS accumulation. The neuro protection therapy attempts to interfere with these few processes by using antioxidants, metal chelators, calcium antagonists or glutamatergic antagonists. In the protocol used in our laboratory, neonatal rats were irradiated with 5 Gy gamma radiations in their cephalic ends, and pre or post-treated with selected putative neuro protective agents. After 30-90 days, motor, morphological and biochemical parameters were measured and compared with irradiated and sham-irradiated (control) animals. Drugs as GM1 ganglioside or amifostine were able to restore abnormal parameters. Cerebellar granule cell irradiated 'in vitro' were treated with neuro protective agents prior or after irradiation. Cell viability and several biochemical parameters were analysed after 48 hours. GM1 ganglioside and amifostine were effective in preventing cell death and increase in ROS induced by ionizing radiation exposure. (author)

  13. A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-Induced Xerostomia in Head and Neck Cancer (Rtog 0244)s

    Science.gov (United States)

    Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R.; McEwan, AJB.; Thomas Robbins, K.; Grecula, John; Sharma, Anand K.; Ang, K. Kian

    2012-01-01

    Purpose We report the results of a phase II study to determine reproducibility of surgical technique of submandibular salivary gland transfer (SGT) for prevention of radiation (XRT) induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials Eligible patients had surgery for primary, neck dissection, and SGT followed by XRT during which the transferred salivary gland was shielded. IMRT, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by two and radiation by one reviewer. If 13 or more (out of 43) were “not per protocol”, then technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, Grade 2 or higher and a rate of ≤ 51% was acceptable. Results 44 of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was “per protocol” or with acceptable variation in 34 patients (77.3%) and XRT in 79.5%. 9 patients (20.9%) developed grade II acute xerostomia; 2 had grade 0 -1 xerostomia (4.7%) but started on amifostine/pilocarpine. These 11 patients (25.6%) were considered failures for the xerostomia endpoint. 13 patients have died; median follow-up for 31 surviving patients is 2.9 years. Two-year overall and disease-free survival rates are 76.4% and 71.7%, respectively. Conclusions the technique of submandibular salivary gland transfer procedure is reproducible in a multicenter setting. Seventy-four percent of patients had prevention of XRT induced acute xerostomia. PMID:22541957

  14. A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-induced Xerostomia in Head-and-Neck Cancer (RTOG 0244)

    International Nuclear Information System (INIS)

    Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R.; McEwan, A.J.B.; Robbins, K. Thomas; Grecula, John; Sharma, Anand K.; Ang, K. Kian

    2012-01-01

    Purpose: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were “not per protocol,” then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤51% was acceptable. Results: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was “per protocol” or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.

  15. A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-induced Xerostomia in Head-and-Neck Cancer (RTOG 0244)

    Energy Technology Data Exchange (ETDEWEB)

    Jha, Naresh, E-mail: naresh.jha@albertahealthservices.ca [University of Alberta, Cross Cancer Institute, Edmonton, Alberta (Canada); Harris, Jonathan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Seikaly, Hadi [University of Alberta, Edmonton, Alberta (Canada); Jacobs, John R. [Wayne State University School of Medicine, Detroit, Michigan (United States); McEwan, A.J.B. [University of Alberta, Cross Cancer Institute, Edmonton, Alberta (Canada); Robbins, K. Thomas [St. John' s Hospital Cancer Institute, Springfield, Illinois (United States); Grecula, John [Ohio State University Medical Center, Columbus, Ohio (United States); Sharma, Anand K. [Medical University of South Carolina, Charleston, South Carolina (United States); Ang, K. Kian [University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-10-01

    Purpose: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were 'not per protocol,' then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of {<=}51% was acceptable. Results: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was 'per protocol' or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.

  16. Mitomycin-Induced Pulmonary Veno-Occlusive Disease: Evidence From Human Disease and Animal Models.

    Science.gov (United States)

    Perros, Frédéric; Günther, Sven; Ranchoux, Benoit; Godinas, Laurent; Antigny, Fabrice; Chaumais, Marie-Camille; Dorfmüller, Peter; Hautefort, Aurélie; Raymond, Nicolas; Savale, Laurent; Jaïs, Xavier; Girerd, Barbara; Cottin, Vincent; Sitbon, Olivier; Simonneau, Gerald; Humbert, Marc; Montani, David

    2015-09-01

    Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension characterized by the obstruction of small pulmonary veins and a dismal prognosis. PVOD may be sporadic or heritable because of biallelic mutations of the EIF2AK4 gene coding for GCN2. Isolated case reports suggest that chemotherapy may be a risk factor for PVOD. We reported on the clinical, functional, and hemodynamic characteristics and outcomes of 7 cases of PVOD induced by mitomycin-C (MMC) therapy from the French Pulmonary Hypertension Registry. All patients displayed squamous anal cancer and were treated with MMC alone or MMC plus 5-fluoruracil. The estimated annual incidence of PVOD in the French population that have anal cancer is 3.9 of 1000 patients, which is much higher than the incidence of PVOD in the general population (0.5/million per year). In rats, intraperitoneal administration of MMC induced PVOD, as demonstrated by pulmonary hypertension at right-heart catheterization at days 21 to 35 and major remodeling of small pulmonary veins associated with foci of intense microvascular endothelial-cell proliferation of the capillary bed. In rats, MMC administration was associated with dose-dependent depletion of pulmonary GCN2 content and decreased smad1/5/8 signaling. Amifostine prevented the development of MMC-induced PVOD in rats. MMC therapy is a potent inducer of PVOD in humans and rats. Amifostine prevents MMC-induced PVOD in rats and should be tested as a preventive therapy for MMC-induced PVOD in humans. MMC-induced PVOD in rats represents a unique model to test novel therapies in this devastating orphan disease. © 2015 American Heart Association, Inc.

  17. Utility of DF-1 for Radioprotection in Lymphocytes

    Science.gov (United States)

    Reynolds, Julia; Casey, Rachael; Wu, Honglu; Huff, Janice; Emami, Kamal; Moore, Valerie; Jeevarajan, Antony

    2007-01-01

    The development of degenerative changes in the vasculature, such as atherosclerosis, is a known consequence of exposure to ionizing radiation, and is thus a concern for astronaut health following long duration space flight. Cellular damage caused by radiation is due to free radical generation and DNA damage. The goal of this project was to assess the ability of a C60-derivative, DF-1, to mitigate cellular damage resulting from radiation exposure in primary human lymphocytes. DF-1 is a water-soluble C60 fullerene encapsulated in dendrimeric functional groups that is proposed to exhibit antioxidant properties. Human lymphocytes are radiosensitive and travel throughout the body potentially causing bystander effects in any tissues they contact. These cells were subjected to varying doses of gamma radiation in the presence or absence of DF-1. Cells were collected at 48 hours post-irradiation for chromosomal aberration studies and at 72 hours post-irradiation for micronuclei studies. These studies showed that the irradiated cells contained more chromosomal aberrations and micronuclei than the control cells. Addition of the DF-1 reduced the amount of observed DNA damage in the irradiated cells. Growth curves were measured for the lymphocytes exposed to 0 and 4 Gray gamma irradiations, and we observed less growth in the cells irradiated at 4 Gy. 2,7-dichlorofluorescein diacetate was used to detect reactive oxygen species production, and increased production of ROS was observed in the irradiated lymphocytes. Human lymphocytes were subjected to varying doses of gamma or photon radiation in the presence and absence of DF-1 and a known radioprotectant, amifostine. After irradiation, the production of reactive oxygen species, growth curves and cell viability were measured. These cells were also collected to quantify chromosomal aberrations and micronuclei formation. We predict that irradiated cells will show the most damage and that DF-1 will provide protective effects similar

  18. A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244).

    Science.gov (United States)

    Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R; McEwan, A J B; Robbins, K Thomas; Grecula, John; Sharma, Anand K; Ang, K Kian

    2012-10-01

    We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were "not per protocol," then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤ 51% was acceptable. Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was "per protocol" or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Tratamento da mucosite em pacientes submetidos a transplante de medula óssea: uma revisão sistemática Tratamiento de la mucositis en pacientes sometidos a transplante de médula ósea: una revisión sistemática Treatment of mucositis in patients undergoing bone marrow transplantation: a systematic review

    Directory of Open Access Journals (Sweden)

    Patrícia Ferreira

    2011-01-01

    Full Text Available OBJETIVO: Identificar as medidas terapêuticas para redução da gravidade da mucosite oral em pacientes adultos submetidos ao Transplante de Medula Óssea (TMO. MÉTODOS: Revisão sistemática nas bases de dados: LILACS, MEDLINE, CINAHL, EMBASE; CENTRAL (Cochrane Central e DARE (Database of abstracts of reviews of effects, no período de 1972 a julho de 2010, utilizando os descritores mucositis, stomatitis e bone-marrow-transplantation. RESULTADOS: Identificaram-se 3.839 resumos, dos quais 22 foram incluídos na revisão sistemática que descreveram 14 intervenções tópicas e sistêmicas, dentre as quais oito com significância estatística para a redução dessa complicação. As terapias tópicas foram a crioterapia, clorexidine, glutamina, laser e Traumeel® e as sistêmicas, amifostine, Granulokine® e palifermin. CONCLUSÃO: A heterogeneidade dos resultados dessas intervenções e a falta de melhor elucidação para a prática assistencial indicam a necessidade de pesquisas mais precisas para identificar a efetividade de terapias tópicas para a reparação celular das mucosas.OBJETIVO: Identificar las medidas terapéuticas para la reducción de la gravedad de la mucositis oral en pacientes adultos sometidos a Transplante de Médula Ósea (TMO. MÉTODOS: Se trata de una revisión sistemática en las bases de datos: LILACS, MEDLINE, CINAHL, EMBASE; CENTRAL (Cochrane Central y DARE (Database of abstracts of reviews of effects, en el período de 1972 a julio del 2010, utilizando los descriptores mucositis, stomatitis y bone-marrow-transplantation. RESULTADOS: Se identificaron 3.839 resúmenes, y de éstos 22 fueron incluídos en la revisión sistemática que describieron 14 intervenciones tópicas y sistémicas, de las cuales ocho con significancia estadística para la reducción de esa complicación. Las terapias tópicas fueron la crioterapia, clorexidine, glutamina, laser y Traumeel® y las sistémicas, amifostine, Granulokine® y

  20. RLIP76 in defense of radiation poisoning.

    Science.gov (United States)

    Singhal, Jyotsana; Singhal, Sharad S; Yadav, Sushma; Suzuki, Sumihiro; Warnke, Molly M; Yacoub, Adly; Dent, Paul; Bae, Sejong; Sharma, Rajendra; Awasthi, Yogesh C; Armstrong, Daniel W; Awasthi, Sanjay

    2008-10-01

    To determine the role of RLIP76 in providing protection from radiation and chemotherapy. In the present report, we used RLIP76 to refer to both the mouse (Ralbp1) and the human (RLIP76) 76-kDa splice variant proteins (RLIP76) for convenience and to avoid confusion. In other reports, Ralbp1 refers to the mouse enzyme (encoded by the Ralbp1 gene), which is structurally and functionally homologous to RLIP76, the human protein encoded by the human RALBP1 gene. Median lethal dose studies were performed in RLIP76(-/-) and RLIP76(+/+) C57B mice after treatment with a single dose of RLIP76 liposomes 14 h after whole body radiation. The radiosensitivity of the cultured mouse embryonic fibroblasts and the effects of buthionine sulfoximine (BSO), amifostine, c-jun N-terminal kinase (JNK), protein kinase B (Akt), and MAPK/ERK kinase (MEK) were determined by colony-forming assays. Glutathione-linked enzyme activities were measured by spectrophotometric assays, glutathione by dithiobis-2-nitrobenzoic acid (DTNB), lipid hydroperoxides by iodometric titration, and aldehydes and metabolites by thiobarbitauric acid reactive substances and liquid chromatography-mass spectrometry (LCMS). RLIP76(-/-) mice were significantly more sensitive to radiation than were the wild-type, and RLIP76 liposomes prolonged survival in a dose-dependent manner in both genotypes. The levels of 4-hydroxynonenal and glutathione-conjugate of 4-hydroxynonenal were significantly increased in RLIP76(-/-) tissues compared with RLIP76(+/+). RLIP76(-/-) mouse embryonic fibroblasts were markedly more radiosensitive than RLIP76(+/+) mouse embryonic fibroblasts, despite increased glutathione levels in the former. RLIP76 augmentation had a remarkably greater protective effect compared with amifostine. The magnitude of effects of RLIP76 loss on radiation sensitivity was greater than those caused by perturbations of JNK, MEK, or Akt, and the effects of RLIP76 loss could not be completely compensated for by modulating

  1. Prevention of chemotherapy-induced nephrotoxicity in children with cancer

    Directory of Open Access Journals (Sweden)

    Fatemeh Ghane Sharbaf

    2017-01-01

    Full Text Available Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL, ifosfamide (IFO, carboplatin, and methotrexate (MTX. Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI, tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS, and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels. CPL, mitomycin C, and gemcitabine treatment cause vascular injury and HUS. High-dose IFO, streptozocin, and azacitidine cause renal tubular dysfunction manifested by Fanconi syndrome, rickets, and osteomalacia. AKI is a common adverse effect of MTX, interferon-alpha, and nitrosourea compound treatment. These strategies to reduce the cytotoxic drug-induced nephrotoxicity should include adequate hydration, forced diuresis, and urinary alkalization. Amifostine, sodium thiosulfate, and diethyldithiocarbamate provide protection against CPL-induced renal toxicity.

  2. Prospective of clinical drugs for radioprotection

    International Nuclear Information System (INIS)

    Alok, Amit; Kumar, Sandeep; Kumar, Arun; Chaudhury, N.K.

    2014-01-01

    We are living in an era of nuclear power where power derived from nuclear reaction is used for power generation as well as for nuclear weapons. The terrorism and the threat of dirty bombs looms around the civilized population. Therefore, there is a need to develop radioprotector which could prevent against the harmful effect of radiation. The research on radioprotector started more than fifty years ago but still there is no approved radioprotector in the drug market. Hundreds of lead molecule have been screened and have shown varying amount of radioprotection either in vitro or in vivo or in both. Only one drug amifostine was approved by FDA but due to its toxicity in head and neck cancer, this drug is no more in use. Antioxidants too have proven to be a potential radioprotector but the dose required for radioprotection is too high for maintenance of homeostasis in physiological system. We have taken an alternative approach of using clinical drugs like diclofenac and tetracycline for development of approach for radioprotection and reported the radioprotective role of diclofenac. The advantage of using clinical drug is its wide availability in the market and the ease with which it could be channelized for radioprotection. Antiradical assays have demonstrated possible use of tetracycline for radioprotection. Tetracycline has also ability to reduce oxidative damages ex vivo. Studies related to comet assay as well as antioxidant assays in different organs are in progress for designing further work for efficacy and elucidation of mechanisms. (author)

  3. Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

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    Jonas Ahlstedt

    2015-12-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

  4. Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard

    Directory of Open Access Journals (Sweden)

    Pankaj Verma

    2014-10-01

    Full Text Available DRDE-07, a newly synthesized amifostine analog currently under clinical investigation in a phase I trial, is a potent antidote against sulfur mustard toxicity. The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg. The physicochemical properties of DRDE-07, including solubility, pKa, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. DRDE-07 concentration was determined by an HPLC-UV method. The profile of plasma concentration versus time was analyzed using a non-compartmental model. Plasma protein binding was assessed using ultrafiltration. DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels (Cmax observed in less than 15 min. There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing. The plasma protein binding of DRDE-07 was found to be less than 25% at all concentrations studied. Plasma clearance of DRDE-07 is expected to be ~1.5 fold higher than the blood clearance of DRDE-07. The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.

  5. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy.

    Science.gov (United States)

    Riley, Philip; Glenny, Anne-Marie; Hua, Fang; Worthington, Helen V

    2017-07-31

    regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded. We used standard methodological procedures expected by Cochrane. We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0

  6. Radio-induced neuropathology: from early effects to late sequelae. Rat behavioural and metabolic studies after sublethal total body irradiation; Neuropathologie radio-induite: des effets precoces aux sequelles tardives. Etudes comportementales et metaboliques chez le rat apres irradiation globale subletale

    Energy Technology Data Exchange (ETDEWEB)

    Martigne, A.P.

    2010-05-15

    The radioresistance dogma of Central Nervous System (CNS) is now obsolete. Recent progress in neuroscience allow us to reconsider the radiation-induced cognitive dysfunctions observed after radiation therapy or after a nuclear accident, and to devise appropriate diagnostic and therapeutic means. We have developed a Rat model to study the effects of total body irradiation at a sublethal dose (4.5 Gy). This leads to impaired learning and memory of a task being acquired during the first month - which is prevented by administration of a radioprotector (amifostine) - while it does not appear to affect retrograde memory. Early, an apoptotic wave occurs in the sub-ventricular zone, 5 to 9 hours after exposure, while neuro-genesis is suppressed. Two days after irradiation, the metabolic study conducted by NMR HRMAS (High Resolution Magic Angle Spinning) suggests the presence of cerebral oedema and the study of brain lipids in liquid NMR confirms the membrane damages (elevated cholesterol and phospholipids). The lipid profile is then normalized while a gliosis appears. Finally, 1 month post-irradiation, the elevation of GABA, an inhibitory neurotransmitter, in 2 separate brain structures, occurs simultaneously with a taurine decrease in the hippocampus that lasts 6 months. Our integrated model allows validating bio-markers measurable in vivo NMR spectroscopy - the next experimental stage - and testing new radiation-protective agents. (author)

  7. Prevention and management of radiation-induced dermatitis, mucositis, and xerostomia.

    Science.gov (United States)

    Radvansky, Lauren J; Pace, Makala B; Siddiqui, Asif

    2013-06-15

    Current strategies for preventing and managing radiation-induced dermatitis, mucositis, and xerostomia are reviewed, with an emphasis on pharmacologic interventions. Nearly two thirds of all patients with cancer receive radiation therapy during the course of treatment, frequently resulting in acute skin and mucosal toxicities. The severity of radiotherapy-associated toxicities varies according to multiple treatment- and patient-related factors (e.g., total radiation dose and dose fractionation schedule, volume of organ or tissue irradiated, use of concurrent versus sequential chemotherapy, comorbid conditions, functional performance status). Three major radiation toxicities encountered in clinical practice are (1) radiation dermatitis, typically managed with a variety of topical agents such as water-based moisturizing creams or lotions, topical steroids, antiinflammatory emulsions, and wound dressings, (2) radiation-induced oral mucositis, which can be managed through proper basic oral care practices, appropriate pain management, and the use of medicated mouthwashes and oral rinses and gels, and (3) radiation-induced xerostomia, which can be alleviated with saliva substitutes, moistening agents, and sialagogues. Pharmacists involved in the care of patients receiving radiotherapy can play an important role in optimizing symptom control, educating patients on self-care strategies, and adverse effect monitoring and reporting. Radiation-induced dermatitis, mucositis, and xerostomia can cause significant morbidity and diminished quality of life. Pharmacologic interventions for the prevention and treatment of these toxicities include topical agents for dermatitis; oral products, analgesics, and palifermin for mucositis; and amifostine, saliva substitutes, and pilocarpine for xerostomia.

  8. The role of saliva in oral health: strategies for prevention and management of xerostomia.

    Science.gov (United States)

    Brosky, Mary Elizabeth

    2007-05-01

    Oral complications are the most frequent and debilitating sequelae of radiation treatment for patients with head and neck cancer. Impaired salivary function and consequent xerostomia can persist for years after radiation treatment, significantly increasing the risk of oral and dental disease and negatively affecting patients' quality of life. Current evidence indicates that many patients undergoing radiation treatment do not receive adequate oral and dental care and follow-up and that patients' compliance with oral care recommendations is frequently poor. Topical lubricants, coating agents,and saliva substitutes or lozenges may provide transient relief from xerostomia. Cholinergic stimulants such as pilocarpine improve salivary flow but have had mixed results in improving patients' assessments of symptoms or other quality-of-life measures. Advances in radiotherapy techniques, such as intensity-modulated radiation therapy, have enabled increased delivery of therapeutic doses of radiation to tumors while limiting exposure to normal tissues, thereby reducing the incidence, duration, and severity of xerostomia in some patients with head and neck cancers. Additionally, radioprotective agents such as amifostine have been shown to reduce radiation-induced toxicity to normal tissues within the radiation field. Studies are ongoing to determine the optimal approaches for these techniques and agents to maximize clinical response while improving the overall quality of life for patients with head and neck cancer.

  9. Radioprotective effects of hawthorn fruit extract against gamma irradiation in mouse bone marrow cells

    International Nuclear Information System (INIS)

    Hosseinimehr, S.J.; Azadbakht, M.; Mousavi, S.M.; Mahmoudzadeh, A.; Akhlaghpoor, S.

    2007-01-01

    The radioprotective effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by gamma irradiation has been investigated in mouse bone marrow cells. A single intraperitoneal (ip) administration of hawthorn extract at doses of 25, 50, 100 and 200 mg/kg 1 h prior to gamma irradiation (2 Gy) reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs). All four doses of hawthorn extract significantly reduced the frequencies of MnPCEs and increased the PCE/PCE+NCE ratio (polychromatic erythrocyte/polychromatic erythrocyte+normochromatic erythrocyte) in mice bone marrow compared with the non drug-treated irradiated control (p<0.02-0.00001). The maximum reduction in MnPCEs was observed in mice treated with extract at a dose of 200 mg/kg. Administration of amifostine at dose 100 mg/kg and hawthorn at dose 200 mg/kg reduced the frequency of MnPCE almost 4.8 and 5.7 fold; respectively, after being exposed to 2 Gy of gamma rays, compare with the irradiated control group. Crataegus extract exhibited concentration-dependent activity on 1, 1-diphenyl 2-picrylhydrazyl free radical showing that Crataegus contained high amounts of phenolic compounds and the high performance liquid chromatography (HPLC) analysis determined that it contained chlorogenic acid, epicatechin and hyperoside. It appeared that hawthorn extract with antioxidant activity reduced the genotoxicity induced by gamma irradiation in bone marrow cells. (author)

  10. Radio-induced neuropathology: from early effects to late sequelae. Rat behavioural and metabolic studies after sublethal total body irradiation

    International Nuclear Information System (INIS)

    Martigne, A.P.

    2010-05-01

    The radioresistance dogma of Central Nervous System (CNS) is now obsolete. Recent progress in neuroscience allow us to reconsider the radiation-induced cognitive dysfunctions observed after radiation therapy or after a nuclear accident, and to devise appropriate diagnostic and therapeutic means. We have developed a Rat model to study the effects of total body irradiation at a sublethal dose (4.5 Gy). This leads to impaired learning and memory of a task being acquired during the first month - which is prevented by administration of a radioprotector (amifostine) - while it does not appear to affect retrograde memory. Early, an apoptotic wave occurs in the sub-ventricular zone, 5 to 9 hours after exposure, while neuro-genesis is suppressed. Two days after irradiation, the metabolic study conducted by NMR HRMAS (High Resolution Magic Angle Spinning) suggests the presence of cerebral oedema and the study of brain lipids in liquid NMR confirms the membrane damages (elevated cholesterol and phospholipids). The lipid profile is then normalized while a gliosis appears. Finally, 1 month post-irradiation, the elevation of GABA, an inhibitory neurotransmitter, in 2 separate brain structures, occurs simultaneously with a taurine decrease in the hippocampus that lasts 6 months. Our integrated model allows validating bio-markers measurable in vivo NMR spectroscopy - the next experimental stage - and testing new radiation-protective agents. (author)

  11. [Medical prevention and treatment of radiation-induced pulmonary complications].

    Science.gov (United States)

    Vallard, A; Rancoule, C; Le Floch, H; Guy, J-B; Espenel, S; Le Péchoux, C; Deutsch, É; Magné, N; Chargari, C

    2017-08-01

    Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  12. Risks and management of radiation exposure.

    Science.gov (United States)

    Yamamoto, Loren G

    2013-09-01

    High-energy ionizing radiation is harmful. Low-level exposure sources include background, occupational, and medical diagnostics. Radiation disaster incidents include radioactive substance accidents and nuclear power plant accidents. Terrorism and international conflict could trigger intentional radiation disasters that include radiation dispersion devices (RDD) (a radioactive dirty bomb), deliberate exposure to industrial radioactive substances, nuclear power plant sabotage, and nuclear weapon detonation. Nuclear fissioning events such as nuclear power plant incidents and nuclear weapon detonation release radioactive fallout that include radioactive iodine 131, cesium 137, strontium 90, uranium, plutonium, and many other radioactive isotopes. An RDD dirty bomb is likely to spread only one radioactive substance, with the most likely substance being cesium 137. Cobalt 60 and strontium 90 are other RDD dirty bomb possibilities. In a radiation disaster, stable patients should be decontaminated to minimize further radiation exposure. Potassium iodide (KI) is useful for iodine 131 exposure. Prussian blue (ferric hexacyanoferrate) enhances the fecal excretion of cesium via ion exchange. Ca-DTPA (diethylenetriaminepentaacetic acid) and Zn-DTPA form stable ionic complexes with plutonium, americium, and curium, which are excreted in the urine. Amifostine enhances chemical and enzymatic repair of damaged DNA. Acute radiation sickness ranges in severity from mild to lethal, which can be assessed by the nausea/vomiting onset/duration, complete blood cell count findings, and neurologic symptoms.

  13. Inhibition of Radiation-Induced Oxidative Damage in the Lung Tissue: May Acetylsalicylic Acid Have a Positive Role?

    Science.gov (United States)

    Demirel, Can; Kilciksiz, Sevil Cagiran; Gurgul, Serkan; Erdal, Nurten; Yigit, Seyran; Tamer, Lulufer; Ayaz, Lokman

    2016-02-01

    The lung is relatively sensitive to irradiation. It is shown that acetylsalicylic acid (ASA) might reduce oxidative injury and that it has a place in protection from cancer. The aim of this study is to evaluate the potential radioprotective effects of ASA. Whole-body irradiation (6 Gy, single dose) was applied to the rats. Glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels in the lung tissue were measured. Control (C), Radiation (R), Radiation + ASA (R + ASA; received irradiation and 25 mg/kg of ASA intraperitoneally (i.p.)), and Radiation + Amifostine (R + WR-2721; received irradiation and 200 mg/kg of WR-2721 i.p.) groups were used. The MPO levels decreased statistically significantly in the group administered ASA. Histopathologically, a radioprotective effect of ASA was more evident in the R + ASA group. ASA is an agent which has not been used as a radioprotector in the clinic yet, and it is worth supporting with more advanced studies.

  14. New strategies for the prevention of radiation injury. Possible implications for countering radiation hazards of long-term space travel

    International Nuclear Information System (INIS)

    Seed, T.; Kumar, S.; Whitnall, M.

    2002-01-01

    New strategies for the prevention of radiation injuries are currently being explored with the ultimate aim of developing globally radioprotective, nontoxic pharmacologics. The prophylactic treatments under review encompass such diverse pharmacologic classes as novel immunomodulators, nutritional antioxidants, and cytokines. An immunomodulator that shows promise is 5-androstenediol (AED), a well-tolerated, long-acting and rostene steroid with broad-spectrum radioprotective attributes that include not only protection against acute tissue injury, but also reduced susceptibility to infectious agents, as well as reduced rates of neoplastic transformation. Other potentially useful radioprotectants currently under study include the nutraceutical vitamin E and analogs, a chemically-engineered cytokine, interleukin-1β, and a sustained-release formulation of an aminothiol, amifostine. Results suggest that a new paradigm is evolving for the prophylaxes of radiation injuries, based on use of newly identified, nontoxic, broad-spectrum prophylactic agents whose protective action may be leveraged by subsequent postexposure use of cytokines with organ-specific reparative functions. (author)

  15. Prophylaxis for mucositis induced by ambulatory chemotherapy: systematic review.

    Science.gov (United States)

    Manzi, Natália de Melo; Silveira, Renata Cristina de Campos Pereira; dos Reis, Paula Elaine Diniz

    2016-04-01

    The aim of this study was to perform a systematic review of clinical trials covering interventions used as prophylaxis for oral mucositis induced by ambulatory antineoplastic chemotherapy. Oral mucositis in patients undergoing chemotherapy is a side effect that can impact the quality of treatment and can interfere with eating and therapeutic adherence. Quantitative systematic review. Relevant databases were searched, from January 2002-July 2013, by using the combination of the keywords mucositis, stomatitis, neoplasms, antineoplastic agents, drug therapy, prevention and control and chemotherapy. Two researchers independently read the titles and abstracts from every cross-reference. The quality of the included studies was analysed by the Jadad Scale and the Cochrane Collaboration Risk of Bias Tool. Data were extracted from the selected studies with a data collection form developed specifically for this purpose. Of the 23 controlled clinical trials that were identified in this study, five articles evaluated the use of oral cryotherapy to prevent oral mucositis and three studies analysed the prophylactic use of glutamine. Interventions of protocols for oral care, palifermin, allopurinol and chlorhexidine were evaluated by two articles each. Interventions of zinc sulphate, amifostine, chewing gum, sucralfate, recombination human intestinal trefoil factor, kefir and vitamin E were evaluated by one article each. There is strong evidence that cryotherapy can prevent oral mucositis arising from ambulatory treatment with 5-flurouracil chemotherapy. Other interventions, although showing positive results in preventing oral mucositis, require further study to confirm their conclusions. © 2015 John Wiley & Sons Ltd.

  16. Radioprotective Effect of Moderate Wine Consumption in Patients With Breast Carcinoma

    International Nuclear Information System (INIS)

    Morganti, Alessio G.; Digesu, Cinzia; Panunzi, Simona; De Gaetano, Andrea; Macchia, Gabriella; Deodato, Francesco; Cece, M. Grazia; Cirocco, Massimo; Di Castelnuovo, Augusto; Iacoviello, Licia; Valentini, Vincenzo; Cellini, Numa; Gaetano, Giovanni de

    2009-01-01

    Purpose: Given the high cost and side effects of radioprotective agents such as amifostine, attention has been focused on potentially equally effective but less expensive and toxic natural substances. We evaluated the potential radioprotective effects of wine in preventing skin toxicity in patients with breast cancer. Methods and Materials: Before treatment, the medical history and habits of patients were assessed and the information recorded in their clinical folders. Patients were divided into three groups based on the dose/fractionation scheme used: control group, 60.4 Gy (standard technique); Modulated Accelerated Radiotherapy in Adjuvant treatment of breast cancer (MARA)-1 protocol group, 44 Gy (concomitant boost to tumoral bed); and MARA-2 protocol group, 60 Gy (concomitant boost to tumoral bed). The impact of the following variables on acute skin toxicity was evaluated by chart review: radiotherapy protocol, planning target volume (PTV), comorbidity (e.g., hypertension and diabetes), hemoglobin level before therapy, adjuvant hormone therapy, adjuvant chemotherapy, cigarette smoking, and drinking habits. Results: The study population consisted of 348 patients. More severe skin toxicity was significantly associated with the radiotherapy protocol (p < 0.001) and median PTV (p = 0.005). In addition, the incidence of acute toxicity of Grade 2 or greater was higher in patients without alcohol intake (38.4% vs. 22.3%, p = 0.021). The daily amount of alcohol intake also influenced the incidence of skin toxicity, with an incidence of 38.4% in patients with no wine intake, 31.8% in patients drinking half a glass per day, 13.6% in patients drinking one glass per day, and 35.0% in patients drinking two glasses per day. Multivariate analysis showed that wine intake, PTV, and radiotherapy protocol were all significantly correlated with acute toxicity. Conclusions: Our results indicate that wine may have a radioprotective effect; however, prospective studies are needed to

  17. Radioprotectors and Tumors: Molecular Studies in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Gayle Woloschak, David Grdina

    2010-03-10

    This proposal investigated effects of radiation using a set of archival tissues. Main interests of this proposal were to investigate effects of irradiation alone or in the presence or radioprotectors; to investigate these effects on different tissues; and to use/develop molecular biology techniques that would be suitable for work with archived tissues. This work resulted in several manuscripts published or in preparation. Approach for evaluation of gene copy numbers by quantitative real time PCR has been developed and we are striving to establish methods to utilize Q-RT-PCR data to evaluate genomic instability caused by irradiation(s) and accompanying treatments. References: 1. Paunesku D, Paunesku T, Wahl A, Kataoka Y, Murley J, Grdina DJ, Woloschak GE. Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine. Int J Radiat Biol. 2008, 84(8):623-34. PMID: 18661379, http://informahealthcare.com/doi/full/10.1080/09553000802241762?cookieSet=1 2. Wang Q, Paunesku T and Woloschak GE. Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades, in press in Radiation and Environmental Biophysics. 3. Alcantara M, Paunesku D, Rademaker A, Paunesku T and Woloschak GE. A RETROSPECTIVE ANALYSIS OF TISSUE TOXICITIES IN B6CF1 MICE IRRADIATED WITH FISSION NEUTRONS OR COBALT 60 GAMMA RAYS: Gender modulates accumulation of tissue toxicities caused by low dose rate fractionated irradiation; in preparation; this document has been uploaded as STI product 4. Wang Q, Paunesku T Wanzer B and Woloschak GE. Mitochondrial gene copy number differences in different tissues of irradiated and control mice with lymphoid cancers; in preparation 5. Wang Q, Raha, S, Paunesku T and Woloschak GE. Evaluation of gene copy number differences in different tissues of irradiated and control mice; in preparation

  18. Why herbals as radioprotectors?

    International Nuclear Information System (INIS)

    Naruka, Kavita

    2012-01-01

    Increasing use of ionizing radiations for diagnostic as well as therapeutic purposes has drawn the attention of many radiobiologists towards the side effects of such exposures. Therefore, it is desirable that the response of the various tissues to radiation exposure be modified to facilitate the beneficial uses of radiations. Modification of radiation response is obtained by means of chemical substances that can significantly decrease the magnitude of response when present in a biological system during irradiation. Work on the development of chemicals to protect biological system from radiation damage was initiated nearly six decades ago with cysteine. Thereafter, several chemical compounds have been screened for their radioprotective efficacy. Among the chemical radioprotectors, S-2(3- amino-propylamino) ethyl phosphorothioic acid (WR-2721) or amifostine is the most thoroughly investigated radioprotective drug. It is a derivative of cysteamine, which produces more radioprotection to normal tissues than tumor tissues. It offers more than twice the protection observed with other members of the same phosphorothioate series. Therefore, it has been recommended for cancer patients to reduce the side effects of radiotherapy and chemotherapy. But the drug has many drawbacks that it is toxic at maximum effective dose, ineffective by oral administration, unable to provide post irradiation protection and costly. No ideal, safe, synthetic radioprotector are available to date. So the search for alternative radioprotectors has been going on, which are nontoxic, orally effective and cheap. A number of medicinal plants evaluated for their radioprotective ability, which have shown protective effects against the deleterious effects of ionizing radiations. The plants and natural products are usually non-toxic, can be orally administered, inexpensive and act through multiple mechanisms due to presence of many chemicals. Therefore, development of radioprotectors from natural sources

  19. Treatment of radiation-induced normal tissue lesions

    International Nuclear Information System (INIS)

    Rezvani, M.

    2003-01-01

    Normal tissue damage is the most important limiting factor in radiotherapy. It must be possible, at least theoretically, to eradicate a localised tumour if a large enough dose of radiation could be delivered to tumour, however, practically, there is always the danger of damaging normal tissues adjacent to the tumour. Factors such as the total radiation dose, overall treatment time, dose per fraction, dose-rate and the effects of changing the irradicated volume of the spinal cord have been examined in order to improve therapeutic ratio in radiotherapy. The majority of these studies have concentrated on optimizing dose fractionation schedules. Only recently have attempts been made to modify this effect by the administration of therapeutic agents after irradiation but before the development of the lesion. Despite this interest the problem still exists. At present there is no effective clinically applied treatment towards radiation-induced normal tissue injury, however, some symptoms for example swelling or pain during inflammatory phase may respond to corticosteroids. There are a number of agents, which have been used experimentally, some clinically, to alleviate radiation damage. The results of these studies are reviewed. A number of substances, generally named Biological Response Modifiers, with diverse mode of actions have been used in post irradiation modification of normal tissue reactions. The effect and mode of action of a number of these treatments are discussed. Classical radioprotectors, that are mainly thiol-containing substances such as Amifostine, are used for prophylaxis and should be administered before or at the time of irradiation. These substances have been deliberately excluded in this article

  20. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  1. An Odyssey of cytoprotective bisbenzimidazole as therapeutic agent for human well being

    International Nuclear Information System (INIS)

    Tandon, Vibha

    2014-01-01

    Radiotherapy is utilized by 80% patients as a part of their treatment to most prevalent disease like cancer. Ionizing radiation causes radiolysis of water, generation of ROS and has deleterious effect penetrating the living tissues resulting in the-transfer of radiation energy to the biological materials. Radioprotectors protect the normal cells from the unwanted radiation damage. Since the beginning of the nuclear era, despite extensive research on the development of radioprotectors from natural and synthetic compounds, success has been limited. The only clinically acceptable radioprotector, amifostine, has inherent dose-limiting toxicities and has therefore stimulated extensive search for nontoxic, effective, and alternative radioprotectors. We have developed a cytoprotective radioprotector DMA, having a bisbenzimidazole nucleus. Relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of NFkB inducing kinase (NIK) as one of the plausible target. Subsequently, over expression and knock down of NIK suggested that DMA affects NFkB inducing kinase mediated phosphorylation of IKKα and IKKβ both alone and in the presence of ionizing radiation. We observed 51% radioprotection in untreated cells that attenuated to 17% in siRNA NIK treated U87 cells at 24h. Further studies concluded that the Coactivation of AKT/NFkB triggered by DMA, is a reason behind protection against ionizing radiation-induced apoptosis of normal cells, and this was consistent with the alteration of DNA-PKcs. Pharmacokinetic (PK) evaluations and bioavailability measurements proved superior in vivo efficacy, higher AUCs, greater residence time of DMA. (author)

  2. Amelioration of radiation stress by antioxidants and prooxidants: role of redox transcription factors

    International Nuclear Information System (INIS)

    Sandur, Santosh Kumar

    2011-01-01

    The development of radiation countermeasures has emerged as a major area of research in radiation biology as ionizing radiation is finding wide applications in power generation, agriculture, food processing, disease diagnosis and therapy. Chemical agents used to alter tissue toxicity of radiation can be broadly divided into three categories based on the time of intervention in relation to radiation. These are: radioprotectors, mitigators, and therapeutic agents. Radiation causes injury to normal tissue by a dynamic process involving generation of reactive oxygen species (ROS), their interactions with bio-molecules, intracellular signaling, cell-to-cell communication, inflammatory responses, tissue repair and cell death. Most of the radiation-induced damage to bio-molecules is caused by the formation of free radicals resulting from the radiolysis of water. However, antioxidants that neutralize free radicals failed to reach clinic. At present, no agent, approved by the U.S. Food and Drug Administration, is available for the treatment of acute radiation syndrome (ARS), although amifostine is approved for prophylaxis of dry mouth (xerostomia) from radiotherapy of head and neck cancers. Therefore, researchers are employing new approaches to ameliorate radiation induced injury. Some of these include use of cytokines, NF-κB (Nuclear factor κB) activators, agents that induce G1 arrest, antibiotics and inhibitors of P53. We have used pro-oxidants to upregulate cytoprotective pathways as a novel strategy to protect against radiation induced hematopoietic syndrome. Different prooxidants including hydrogen peroxide, diethylmaleate, t-butylhydroperoxide and naphthoquinone and its derivatives protected lymphocytes against radiation induced cell death. Further studies were carried out with 1,4-naphthoquinone (NQ) to explore the molecular mechanism of the observed protection. Thiol containing antioxidants abrogated NQ mediated radioprotection in lymphocytes. Addition of NQ to

  3. DF-1, A Nontoxic Carbon Fullerene Based Antioxidant, is Effective as a Biomedical Countermeasure Against Radiation

    Science.gov (United States)

    Theriot, Corey A.; Casey, Rachael; Conyers, Jodie; Wu, Honglu

    2010-01-01

    A long-term goal of radiation research is the mitigation of inherent risks of radiation exposure. Thus the study and development of safe agents, whether biomedical or dietary, that act as effective radioprotectors is an important step in accomplishing this long-term goal. Some of the most effective agents to date have been aminothiols and their derivatives. Unfortunately, most of these agents have side effects such as nausea, vomiting, hypotension, weakness, and fatigability. For example, nausea and emesis occur in most patients treated with WR-2721 (Amifostine), requiring the use of effective antiemetics, with hypotension being the dose-limiting side effect in patients treated. Clearly, the need for a radioprotector that is both effective and safe still exists. Development of biocompatible nano-materials for radioprotection is a promising emerging technology that could be exploited to address the need to minimize biological effects when exposure is unavoidable. Testing free radical scavenging nanoparticles for potential use in radioprotection is exciting and highly relevant. Initial investigations presented here demonstrate the ability of a particular functionalized carbon fullerene nanoparticle, (DF-1), to act as an effective radioprotector. DF-1 was first identified as the most promising candidate in a screen of several functionalized carbon fullerenes based on lack of toxicity and antioxidant therapeutic potential against oxidative injuries (i.e. organ reperfusion and ionizing radiation). Subsequently, DF-1 has been shown to reduce chromosome aberration yield and cell death, as well as overall ROS levels in human lymphocytes and fibroblasts after exposure to gamma radiation and energetic protons while demonstrating no associated toxicity. The dose-reducing factor of DF-1 at LD50 is nearly 2.0 for gamma radiation. In addition, DF-1 treatment also significantly prevented cell cycle arrest after exposure. Finally, DF-1 markedly attenuated COX2 upregulation in cell

  4. Radioprotectors in Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nair, C.K.K. [Bhabha Atomic Research Centre, Mumbai (India); Parida, D.K.; Nomura, Taisei

    2001-03-01

    This review article focuses on clinically relevant radioprotectors and their mechanisms of radioprotection. Radiotherapy is the most common modality of human cancer therapy. Obtaining optimal results requires a judicious balance between the total dose of radiotherapy delivered and the threshold limit of critical surrounding normal tissues, and the normal tissues need to be protected against radiation injury to obtain better tumor control by using a higher dose. For this reason, radiation-protective agents play an important role in clinical radiotherapy. Radiation-protective agents can be classified into three groups: radioprotectors, adaptogens, and absorbents. The first group generally consists of sulfhydryl compounds and other antioxidants. They include several myelo-, entero-, and cerebro-protectors. Adaptogens act as promotors of radioresistance. They are natural protectors that offer chemical protection against low levels of ionizing radiation. Absorbents protect organs from internal radiation and chemicals. They include drugs that prevent incorporation of radioiodine by the thyroid gland and absorption of radionuclides. This article thoroughly describes the properties, mechanisms of action, and perspectives on clinical application of the following categories of radioprotectors: sulfhydryl compounds (e.g., cysteine, cysteamine, glutathione, AET, WR 2127, and other WR-compounds), antioxidants (e.g., tempace, Hoechst 33342, vitamin A, E, and C, TMG, melatonin), angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, elanopril, penicillamine, pentoxifylline, L-158, 809), cytoprotective agents (mesna, dexrazoxane, and amifostin), metalloelements (e.g., manganese chloride, cadmium salts, bismuth subnitrate), immunomodulators (gamma-interferon, polysaccharides AM5, AM218, heat-killed lactobacillus cells, broncho-vaxom, trehalose dicorynomycolate, and AS101), lipopolysaccharides and prostaglandins, plant extracts and compounds isolated from plants (curcmin

  5. A survey of techniques to reduce and manage external beam radiation-induced xerostomia in British oncology and radiotherapy departments

    Energy Technology Data Exchange (ETDEWEB)

    Macknelly, Andrew [Norfolk and Norwich University Hospital (United Kingdom); Day, Jane [Faculty of Health, Wellbeing and Science, University Campus Suffolk, Waterfront Building, Neptune Quay, Ipswich (United Kingdom)], E-mail: j.day@ucs.ac.uk

    2009-11-15

    Xerostomia is the most common side effect of external beam radiotherapy to the head and neck [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et-al. Can dose reduction to one parotid gland prevent xerostomia? - A feasibility study for locally advanced head and neck cancer patients treated with intensity-modulated radiotherapy. Clinical Oncology 2006;18(6):497-504.]. A survey was carried out in British oncology departments to determine what treatment regimes, to minimise xerostomia, are used for patients with head-and-neck cancers treated with external beam radiotherapy. A semi-structured questionnaire consisting of both quantitative and qualitative questions was designed that asked departments which of the identified methods they used, why a method might not be currently employed, and whether its use had ever been considered. The study found that there are wide disparities between the techniques employed by oncology departments to avoid and reduce xerostomia in patients with cancers of the head and neck. The National Institute of Clinical Health and Excellence, [National Institute for Clinical Health and Excellence (NICE). Improving outcomes in head and neck cancers: the manual. London: Office of Public Sector Information; 2004.] for example, recommends that patients are given dental care and dietary advice but some departments did not appear to be doing this. Less than half of departments stated that they offer complementary therapies and less than 40% prescribed pilocarpine, a saliva-stimulant. Only two respondents stated that they use amifostine, a radioprotector, during radiotherapy treatment to the head and neck. The results also suggested a move toward using Intensity Modulated Radiotherapy (IMRT) for treating head-and-neck cancers which offers better normal tissue sparing than three-dimensional conformal radiotherapy. [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et al. Can dose reduction to one parotid gland prevent xerostomia

  6. A survey of techniques to reduce and manage external beam radiation-induced xerostomia in British oncology and radiotherapy departments

    International Nuclear Information System (INIS)

    Macknelly, Andrew; Day, Jane

    2009-01-01

    Xerostomia is the most common side effect of external beam radiotherapy to the head and neck [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et-al. Can dose reduction to one parotid gland prevent xerostomia? - A feasibility study for locally advanced head and neck cancer patients treated with intensity-modulated radiotherapy. Clinical Oncology 2006;18(6):497-504.]. A survey was carried out in British oncology departments to determine what treatment regimes, to minimise xerostomia, are used for patients with head-and-neck cancers treated with external beam radiotherapy. A semi-structured questionnaire consisting of both quantitative and qualitative questions was designed that asked departments which of the identified methods they used, why a method might not be currently employed, and whether its use had ever been considered. The study found that there are wide disparities between the techniques employed by oncology departments to avoid and reduce xerostomia in patients with cancers of the head and neck. The National Institute of Clinical Health and Excellence, [National Institute for Clinical Health and Excellence (NICE). Improving outcomes in head and neck cancers: the manual. London: Office of Public Sector Information; 2004.] for example, recommends that patients are given dental care and dietary advice but some departments did not appear to be doing this. Less than half of departments stated that they offer complementary therapies and less than 40% prescribed pilocarpine, a saliva-stimulant. Only two respondents stated that they use amifostine, a radioprotector, during radiotherapy treatment to the head and neck. The results also suggested a move toward using Intensity Modulated Radiotherapy (IMRT) for treating head-and-neck cancers which offers better normal tissue sparing than three-dimensional conformal radiotherapy. [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et al. Can dose reduction to one parotid gland prevent xerostomia

  7. Antiradiation vaccine: Technology and development of prophylaxis, prevention and treatment of biological consequences from Heavy Ion irradiation.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Vecheslav

    Introduction: An anti-radiation vaccine could be an important part of a countermeasures reg-imen for effective radioprotection, immunoprophylaxis and immunotherapy of the acute radi-ation syndromes (ARS) after gamma-irradiation, neutron irradiation or heavy ion irradiation. Reliable protection of non-neoplastic regions of patients with different forms of cancer which undergo to heavy ion therapy ( e.g. Hadron-therapy) can significantly extend the efficiency of the therapeutic course. The protection of cosmonauts astronauts from the heavy ion ra-diation component of space radiation with specific immunoprophylaxis by the anti-radiation vaccine may be an important part of medical management for long term space missions. Meth-ods and experiments: 1. The Antiradiation Vaccine preparation -standard (mixture of toxoid form of Radiation Toxins -SRD-group) which include Cerebrovascular RT Neurotoxin, Car-diovascular RT Neurotoxin, Gastrointestinal RT Neurotoxin, Hematopoietic RT Hematotoxin. Radiation Toxins Specific Radiation Determinant Group were isolated from a central lymph of gamma-irradiated animals with Cerebrovascular, Cardiovascular, Gastrointestiinal, Hematopoi-etic forms of ARS. Devices for γ-radiation are "Panorama", "Puma". 2. Heavy ion exposure was accomplished at Department of Scientific Research Institute of Nuclear Physics, Dubna, Russia. The heavy ions irradiation was generated in heavy ion (Fe56) accelerator -UTI. Heavy Ion linear transfer energy -2000-2600 KeV mkm, 600 MeV U. Absorbed Dose -3820 Rad. 3. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A -control -10 rabbits; Group B -placebo -5 rabbits; Group C -radioprotectant Cystamine (50 mg kg)-5 rabbits, 15 minutes before irradiation -5 rabbits; Group D -radioprotectant Gammafos (Amifostine -400mg kg ), -5 rabbits; Group E -Antiradiation Vaccine: subcuta-neus administration or IM -2 ml of active substance, 14 days before irradiation -5 rabbits. 4

  8. Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers.

    Science.gov (United States)

    Lawrie, Theresa A; Green, John T; Beresford, Mark; Wedlake, Linda; Burden, Sorrel; Davidson, Susan E; Lal, Simon; Henson, Caroline C; Andreyev, H Jervoise N

    2018-01-23

    balloon and hydrogel spacers suggests that these interventions for prostate cancer RT may make little or no difference to GI outcomes.Pharmacological interventions: Evidence for any beneficial effects of aminosalicylates, sucralfate, amifostine, corticosteroid enemas, bile acid sequestrants, famotidine and selenium is of a low or very low certainty. However, evidence on certain aminosalicylates (mesalazine, olsalazine), misoprostol suppositories, oral magnesium oxide and octreotide injections suggests that these agents may worsen GI symptoms, such as diarrhoea or rectal bleeding.Non-pharmacological interventions: Low-certainty evidence suggests that protein supplements (RR 0.23, 95% CI 0.07 to 0.74; participants = 74; studies = 1), dietary counselling (RR 0.04, 95% CI 0.00 to 0.60; participants = 74; studies = 1) and probiotics (RR 0.43, 95% CI 0.22 to 0.82; participants = 923; studies = 5; I 2 = 91%) may reduce acute RT-related diarrhoea (grade 2+). Dietary counselling may also reduce diarrhoeal symptoms in the long term (at five years, RR 0.05, 95% CI 0.00 to 0.78; participants = 61; studies = 1). Low-certainty evidence from one study (108 participants) suggests that a high-fibre diet may have a beneficial effect on GI symptoms (mean difference (MD) 6.10, 95% CI 1.71 to 10.49) and quality of life (MD 20.50, 95% CI 9.97 to 31.03) at one year. High-certainty evidence indicates that glutamine supplements do not prevent RT-induced diarrhoea. Evidence on various other non-pharmacological interventions, such as green tea tablets, is lacking.Quality of life was rarely and inconsistently reported across included studies, and the available data were seldom adequate for meta-analysis. Conformal radiotherapy techniques are an improvement on older radiotherapy techniques. IMRT may be better than 3DCRT in terms of GI toxicity, but the evidence to support this is uncertain. There is no high-quality evidence to support the use of any other prophylactic intervention evaluated. However