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  • 1
    Language: English
    In: Oncology Research and Treatment, February 2013, Vol.36(1), pp.2-10
    Keywords: Paper ; Medicine
    ISBN: 9783318023732
    ISBN: 3318023736
    ISSN: 2296-5270
    ISSN: 0378584X
    E-ISSN: 2296-5262
    E-ISSN: 14230240
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  • 2
    In: British Journal of Haematology, October 2012, Vol.159(1), pp.67-77
    Description: The efficacy of bendamustine chlorambucil in a phase trial of previously untreated patients with inet stage chronic lymphocytic leukaemia () was re‐evaluated after a median observation time of 54 months in ay 2010. Overall survival () was analysed for the first time. At follow‐up, investigator‐assessed complete response () rate (21·0% vs 10·8%), median progression‐free survival (21·2 vs 8·8 months; 65 years, responders and non‐responders. However, patients with objective response or a experienced a significantly longer than non‐responders or those without a . Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78·3% vs 63·6%; =0·004). The benefits of bendamustine over chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than chlorambucil in previously untreated patients, with the achievement of a or objective response appearing to prolong . Bendamustine should be considered as a preferred first‐line option over chlorambucil for patients ineligible for fludarabine, cyclophosphamide and rituximab.
    Keywords: Bendamustine ; Chlorambucil ; Chronic Lymphocytic Leukaemia ; Complete Response ; Overall Survival
    ISSN: 0007-1048
    E-ISSN: 1365-2141
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  • 3
    Language: English
    In: Drug metabolism and disposition: the biological fate of chemicals, July 2005, Vol.33(7), pp.984-92
    Description: The alkylating agent bendamustine is currently in phase III clinical trials for the treatment of hematological malignancies and breast, lung, and gastrointestinal tumors. Renal elimination mainly as the parent compound is thought to be the primary route of excretion. Because polar biliary conjugates were expected metabolites of bendamustine, three cysteine S-conjugates were synthesized, purified by quantitative high-performance liquid chromatography (HPLC), and characterized by NMR spectroscopy and mass spectrometry (MS). HPLC assays with MS, as well as fluorescence detection of bile, urine, and plasma after single-dose intravenous infusion of 140 mg/m(2) bendamustine in five subjects with cholangiocarcinoma, indicated the existence of these phase II metabolites, which were identified as cysteine S-conjugates by comparison with the previously characterized synthetic reference standards. The sum of the three cysteine S-conjugates of bendamustine was determined in human bile and urine to be 95.8 and 26.0%, respectively, expressed as mean percentage of the sum of the parent compound and identified metabolites. The percentage of administered dose recovered in urine as cysteine S-conjugates ranged from 0.9 to 4.1%, whereas the total percentage of the administered dose excreted in urine as the parent drug and seven metabolites ranged from 3.8 to 16.3%. The identification of cysteine S-conjugates provide evidence that a major route of bendamustine metabolism in humans involves conjugation with glutathione. Results indicate the importance of phase II conjugation in the elimination of bendamustine, besides phase I metabolism and hydrolytic degradation, and require further investigation.
    Keywords: Bile -- Metabolism ; Cholangiocarcinoma -- Metabolism ; Nitrogen Mustard Compounds -- Metabolism
    ISSN: 0090-9556
    E-ISSN: 1521009X
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  • 4
    Language: English
    In: Blood, Vol.114, pp.934-935
    Keywords: Medicin Och Hälsovetenskap ; Klinisk Medicin ; Hematologi ; Medical And Health Sciences ; Clinical Medicine ; Hematology
    ISSN: 1528-0020
    ISSN: 00064971
    Source: SwePub (National Library of Sweden)
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  • 5
    In: Anti-Cancer Drugs, 2007, Vol.18(5), pp.587-595
    Description: The present phase I trial was planned to assess the maximum tolerated dose, the dose-limiting toxicity and the pharmacokinetics of bendamustine hydrochloride in a once every 3 weeks schedule, and to recommend a safe dose for future phase II studies. Included were patients with refractory solid tumors. Bendamustine hydrochloride was administered as a short intravenous infusion over 30 min. The starting dose was defined at 160 mg/m and dose escalation used increments of 20 mg/m. Plasma and urine samples were analyzed using validated high-pressure liquid chromatography/fluorescence assays. Twenty-six patients (14 men, 12 women) were enrolled for the study. At 280 mg/m, one out of four patients developed a thrombocytopenia grade 4, two experienced grade 3 fatigue and three experienced cardiac toxicity (grade 2). The latter toxicity was considered dose limiting also and further dose escalation was stopped. Plasma pharmacokinetics parameters of bendamustine hydrochloride and its metabolites were assessed in 15 patients. Mean pharmacokinetic parameters of bendamustine hydrochloride were a tmax of 32.3 min, a t1/2 of 37.8 min, a volume of distribution of 14.2 l/m and a clearance of 287.8 ml/min/m. No dose dependency of bendamustine hydrochloride was observed within the used dose range. The metabolites comprised only 23% of the overall area under the concentration–time curve. The maximum tolerated dose of bendamustine hydrochloride on day 1 q 3 weeks is 280 mg/m. Fatigue and cardiac toxicity were dose limiting. The plasma pharmacokinetics data of bendamustine and its metabolites were in accordance with previous reports. The recommended dose for future trials is 260 mg/m every 3 weeks.
    Keywords: Antineoplastic Agents -- Administration & Dosage ; Neoplasms -- Drug Therapy ; Nitrogen Mustard Compounds -- Administration & Dosage;
    ISSN: 0959-4973
    E-ISSN: 14735741
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  • 6
    Language: English
    In: Blood, Vol.112, pp.728-728
    Keywords: Medicin Och Hälsovetenskap ; Klinisk Medicin ; Hematologi ; Medical And Health Sciences ; Clinical Medicine ; Hematology
    ISSN: 1528-0020
    ISSN: 00064971
    Source: SwePub (National Library of Sweden)
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  • 7
    Language: English
    In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 10 September 2009, Vol.27(26), pp.4378-84
    Description: This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL). Patients (〈or= 75 years of age) were randomly assigned to receive bendamustine 100 mg/m(2)/d intravenously on days 1 to 2, or chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee. A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P 〈 .0001). More patients showed complete responses with bendamustine than with chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P 〈 .0001). Bendamustine was also associated with an improvement in duration of remission, compared with chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients. Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.
    Keywords: Chlorambucil -- Therapeutic Use ; Leukemia, Lymphocytic, Chronic, B-Cell -- Drug Therapy ; Nitrogen Mustard Compounds -- Therapeutic Use
    E-ISSN: 1527-7755
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  • 8
    Language: English
    In: European Journal of Cancer and Clinical Oncology, 1989, Vol.25(6), pp.933-937
    Description: Between 1982 and 1987 a prospectively randomized trial of sequential hemibody irradiation (SHBI) (A), a non-cross-resistant chemotherapy drug combination (B) and local and/or locoregional radiotherapy (C) in small cell lung cancer (SCLC) was conducted. Previously untreated patients with extensive SCLC were randomized into three arms: A = 31 patients, B = 37, C = 31. In the chemotherapy combination, the following were used: etoposide, doxorubicin, methotrexate (VAM) and procarbacine, vincristine, cyclophosphamide, lomustine (POCC) and prophylactic cranial irradiation (30 Gy). The results show that the median survival was significantly (P less than 0.01) better in chemotherapy (44 weeks) compared with 17 and 20 weeks in arms A and C, respectively. One year and 2 year survival rates were better for the chemotherapy arm. No differences were found between groups A and C. In comparing the total hospitalization time expressed as a percentage of overall survival, an advantage for group B was shown. In conclusion, high dose SHBI cannot be recommended as a standard therapy for extensive SCLC.
    Keywords: Medicine
    ISSN: 0277-5379
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  • 9
    In: Contrast Media & Molecular Imaging, March 2012, Vol.7(2), pp.204-213
    Description: The development of magnetic resonance imaging (MRI) contrast agents targeting epitopes in atherosclerosis is of general interest. In particular, early detection of activated platelets as key players in plaque rupture could provide improved triage of patients. However, so far the efficiency of contrast agents targeting human pathologies can only be examined in animal experiments, which do not necessarily reflect human conditions. We therefore describe application of a contrast agent targeting activated human platelets in an MRI tissue flow chamber, allowing detection and characterization of contrast agent binding. Microparticles of iron oxide (MPIO) were conjugated to an antibody targeting ligand‐induced binding sites (LIBS) on the activated platelet glycoprotein IIb/IIIa‐receptor or to control antibody, resulting in LIBS–MPIO or control–MPIO contrast agent. Human endarterectomy specimens from patients with acute stroke or transient ischemic attack were imaged before and after contrast agent perfusion using a 9.4 T MRI system. Specimens were measured under static ( 18) or flow conditions ( 18) in a specially designed flow chamber setup, simulating physiological conditions in a stenosed vessel. A significant MPIO‐induced negative contrast was achieved in MRI by LIBS–MPIO in specimens under static and flow conditions (LIBS–MPIO vs control–MPIO:  〈 0.01), and the location of LIBS–MPIO binding corresponded well between histology and MRI ( 〈 0.05). The number of MPIOs per platelet area on endarterectomy specimens in histology was significantly higher with LIBS–MPIO ( 〈 0.001). Furthermore, the intensity of contrast agent binding and signal change showed the potential to reflect the severity of clinical symptoms. LIBS–MPIO allows the detection of activated platelets on the surface of symptomatic atherosclerotic human plaques using molecular MRI. Furthermore, the MRI tissue flow chamber setup described could help to evaluate binding properties of contrast agents, and might therefore be an interesting tool for contrast agent development from animal experiments towards clinical application. Copyright © 2012 John Wiley & Sons, Ltd. We established molecular MRI of human endarterectomy specimes, allowing detection of activated platelets on the surface of symptomatic plaques by using a platelet‐specific contrast agent in a newly constructed setup of an MRI tissue flow chamber, simulating physiological flow conditions inside the specimen. As a perspective, the flow chamber approach described in this study could help to evaluate binding properties of contrast agents, which seem to qualify for human applications after successful use in animal studies, and might therefore be an interesting tool for contrast agent development towards its clinical application.
    Keywords: Magnetic Resonance Imaging ; Platelets ; Atherosclerosis ; Carotid Endarterectomy
    ISSN: 1555-4309
    E-ISSN: 1555-4317
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  • 10
    Language: English
    In: 2013 European Microwave Conference, October 2013, pp.116-119
    Description: This paper presents the design of vertical chip-to-chip interconnects for mm-wave system-in-package (SiP) applications up to 170 GHz. Solid and liquid type polymer materials are used as the interlayer dielectric on the structured Si-wafers to realize coplanar waveguide (CPW) interconnects. Coplanar transmission lines fabricated on high- and low-resistivity silicon substrates are tested and their characteristics are compared, as well. The interconnect structures show excellent electrical performance from DC up to 170 GHz with an insertion loss of 0.6 dB per transition at 170 GHz.
    Keywords: Substrates ; Packaging ; Mmics ; Gold ; Silicon ; Millimeter Wave Devices ; Packaging ; Millimeter-Wave Integrated Circuits ; Engineering
    Source: IEEE Conference Publications
    Source: IEEE Xplore
    Source: IEEE Journals & Magazines 
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