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  • 1.
    Barlesi, F
    et al.
    University Aix Marseille 2.
    Pazzola, A
    NN Blokhin Russian Canc Research Centre.
    Grossi, F
    Natl Institute Canc Research, Genoa, Italy .
    Kohler, M
    Dr M Koehler Gmbh.
    Mezger, J
    St Vincentius Kliniken Karlsruhe.
    Peters, F J
    Orbis Med Centre.
    Trigo Perez, J M
    Hospital Clin University Virgen Victoria.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Groen, H J M
    University Med Centre Groningen.
    MAINTENANCE BEVACIZUMAB (BV) WITH OR WITHOUT PEMETREXED (PEM) FOLLOWING FIRST-LINE BV-CISPLATIN (CIS)-PEM IN PATIENTS (PTS) WITH ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC): PRELIMINARY SAFETY DATA FROM AVAPERL1 (MO22089) in ANNALS OF ONCOLOGY, vol 21, issue , pp 144-1442010In: ANNALS OF ONCOLOGY, Oxford University Press , 2010, Vol. 21, p. 144-144Conference paper (Refereed)
    Abstract [en]

    n/a

  • 2.
    Barlesi, Fabrice
    et al.
    Hop Marseille, AP HP, Marseille, France.
    Scherpereel, Arnaud
    Univ Lille, Ctr Hosp Reg, Hop A Calmette, Lille, France.
    Rittmeyer, Achim
    Lungenfachklin Immenhausen, Immenhausen, Germany.
    Pazzola, Antonio
    Osped Civile Santissima, Sassari, Italy.
    Ferrer Tur, Neus
    Hosp Son Llatzer, Palma De Mallorca, Spain.
    Kim, Joo-Hang
    Yonsei Univ, Coll Med, Seoul 120749, South Korea.
    Ahn, Myung-Ju
    Sungkyunkwan Univ, Sch Med, Seoul, South Korea.
    Aerts, Joachim G J V
    Amphia Hosp, Breda, Netherlands.
    Gorbunova, Vera
    NN Blokhin Canc Res Ctr Russia, Moscow, Russia.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Wong, Elaine K
    F Hoffmann Roche, Basel, Switzerland.
    Perez-Moreno, Pablo
    F Hoffmann Roche, Basel, Switzerland.
    Mitchell, Lada
    F Hoffmann Roche, Basel, Switzerland.
    Groen, Harry J M
    Univ Med Ctr Groningen, Groningen, Netherlands.
    Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089).2013In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, no 24, p. 3004-3011Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Maintenance therapy is associated with improved survival in patients with non-small-cell lung cancer (NSCLC), but few studies have compared active agents in this setting. AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment.

    PATIENTS AND METHODS: Patients with advanced nonsquamous NSCLC received first-line bevacizumab 7.5 mg/kg, cisplatin 75 mg/m(2), and pemetrexed 500 mg/m(2) once every 3 weeks for four cycles. Those achieving response or stable disease were randomly assigned at a ratio of 1:1 to maintenance bevacizumab 7.5 mg/kg or bevacizumab 7.5 mg/kg plus pemetrexed 500 mg/m(2) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) after random assignment.

    RESULTS: In total, 376 patients received induction treatment, 71.9% achieved disease control, and 67.3% were randomly assigned to maintenance therapy, with 125 and 128 receiving single-agent bevacizumab and bevacizumab plus pemetrexed treatment, respectively. At a median follow-up of 8.1 months, PFS from random assignment was significantly improved in the bevacizumab plus pemetrexed arm (median, 3.7 v 7.4 months; hazard ratio, 0.48; 95% CI, 0.35 to 0.66; P < .001) per a stratified model. The PFS benefit extended across age, performance status, smoking history, and induction response (stable disease v partial response) subgroups. Any grade, grade ≥ 3, and serious adverse events occurred more often with bevacizumab plus pemetrexed maintenance. No new safety signals were observed.

    CONCLUSION: In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.

  • 3.
    Hillerdal, Gunnar
    et al.
    Karolinska University Hospital.
    Benn Sorensen, Jens
    National University Hospital, Copenhagen.
    Sundstrom, Stein
    Regional Hospital, Trondheim, Norway.
    Riska, Henrik
    Helsinki University Hospital.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hjerpe, Anders
    Karolinska University Hospital.
    Treatment of Malignant Pleural Mesothelioma with Carboplatin, Liposomized Doxorubicin, and Gemcitabine A Phase II Study2008In: JOURNAL OF THORACIC ONCOLOGY, ISSN 1556-0864, Vol. 3, no 11, p. 1325-1331Article in journal (Refereed)
    Abstract [en]

    Background: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination or liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study.

    Methods: From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-Lip, but all the others were followed for at least 4 years or until death.

    Results: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median Survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months.

    Conclusion: The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long Survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" Surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.

  • 4.
    Hillerdal, Gunnar
    et al.
    Karolinska University Hospital, Lung Diseases, Solna, Stockholm.
    Benn Sorensen, Jens
    Finsen Institute, Department of Oncology, National University Hospital/Finsen Institute, Copenhagen, Denmark.
    Sundström, Stein
    Regional Hospital, Trondheim, Norway.
    Vikström, Anders
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine UHL. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Treatment of malignant pleural mesothelioma with liposomized doxorubicine: prolonged time to progression and good survival. A Nordic study2008In: The Clinical Respiratory Journal, ISSN 1752-6981, Vol. 2, no 2, p. 80-85Article in journal (Refereed)
    Abstract [en]

    Introduction: Malignant pleural mesothelioma (MPM) has a poor prognosis and there is limited effect of treatment. Lately, pemetrexed and cisplatin have been established as the standard treatment.

    Objectives: The present study was planned in 1998, when there was no standard treatment. Single-dose doxorubicine had, in small studies, accomplished remissions, and the Scandinavian Mesothelioma Groups therefore decided to test a liposomized form of this drug, which had shown limited toxicity but good efficacy in a few small studies.

    Methods: Fifty-four evaluable patients with histologically verified and inoperable MPM were treated with liposomized doxorubicine 40 mg/m2, every 4 weeks for six cycles.

    Results: In all, 29 patients (54%) received at least six treatments. The quality of life remained good during the study. Hematologic toxicity was very low. Palmo–plantar erythema occurred in 11 patients (20%), thereof 7 grade II but none was severe and none was dose-limiting. There were four partial responses (7%). The median time to progression (TTP) was 5 months, the median survival was 12 months, and at 24 months, 22% were still alive.

    Conclusion: Liposomized doxorubicine has a low toxicity and is well tolerated; there were a remarkably long TTP and a good survival. Thus, despite the low response rate, liposomized doxorubicine remains an interesting drug for the treatment of malignant mesothelioma.

  • 5.
    Hillerdal, Gunnar
    et al.
    Karolinska Hospital.
    Sorensen, Jens-Benn
    National University Hospital, Copenhagen.
    Sundström, Stein
    Regional Hospital, Trondheim.
    Riska, Henrik
    Helsinki University Hospital .
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Malignant mesothelioma: prognosis not as bad as generally believed2007In: Journal of Thoracic Oncology. 12<SP>th</SP> World Conference on Lung Cancer, Seoul, Korea, September 2-6, 2007.   2(8) (Supplement 4):S599-S600, August 2007, 2007, p. 599-600Conference paper (Other academic)
  • 6.
    Karlsson, Anna
    et al.
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Cirenajwis, Helena
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Ericson-Lindquist, Kajsa
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Pathology, Regional Laboratories Region Skåne, Lund, Sweden.
    Brunnstrom, Hans
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Pathology, Regional Laboratories Region Skåne, Lund, Sweden.
    Reutersward, Christel
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Jönsson, Mats
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Ortiz-Villalon, Cristian
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Hussein, Aziz
    Department of Pathology and cytology, Sahlgrenska university hospital, Gothenburg, Sweden.
    Bergman, Bengt
    Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Monsef, Nastaran
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Branden, Eva
    Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    Koyi, Hirsh
    Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    de Petris, Luigi
    Thoracic Oncology Unit, Karolinska University Hospital and Department Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Micke, Patrick
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Patthey, Annika
    Department of Pathology, Umeå University Hospital, Umeå, Sweden.
    Behndig, Annelie F.
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden.
    Johansson, Mikael
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Planck, Maria
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden; Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund, Sweden.
    Staaf, Johan
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5207Article in journal (Refereed)
    Abstract [en]

    Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.

  • 7.
    Lal, R.
    et al.
    Guys and St Thomas NHS Fdn Trust, England.
    Hillerdal, G. N.
    Karolinska University of Jukhuset, Sweden.
    Shah, R. N. H.
    Maidstone and Tunbridge Wells NHS Trust, England.
    Crosse, B.
    Calderdale and Huddersfield NHS Trust, England.
    Thompson, J.
    Birmingham Heartlands Hospital, England.
    Nicolson, M.
    Aberdeen Royal Infirm, Scotland.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Potter, V. A.
    Nottingham University Hospital NHS Trust, England.
    Visseren-Grul, C.
    Eli Lilly and Co, IN USA.
    Lorenzo, M.
    Eli Lilly and Co, IN USA.
    Dyachkova, Y.
    Eli Lilly and Co, IN USA.
    Bourayou, N.
    Eli Lilly and Co, IN USA.
    Summers, Y. J.
    Christie Hospital NHS Fdn Trust, England.
    Feasibility of home delivery of pemetrexed in patients with advanced non-squamous non-small cell lung cancer2015In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 89, no 2, p. 154-160Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the feasibility and adherence to home delivery (HD) of pemetrexed maintenance treatment in patients with advanced non-squamous non-small cell lung cancer (nsqNSCLC). Materials and methods: Exploratory, prospective, single-arm, Phase II study in advanced nsqNSCLC patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 that did not progress after 4 first-line induction cycles of a platinum doublet. The first cycle of pemetrexed (500 mg/m(2)) was hospital administered, further cycles were HD until progressive disease or discontinuation. Feasibility was assessed by the adherence rate to HD (probability of reversion to hospital administration or treatment discontinuation due to HD) as primary endpoint, and by health-related quality-of-life (HRQoL: EQ-5D, lung cancer symptom scale [LCSS]), satisfaction with HD, overall survival (OS), and safety. Results: 52 patients (UK and Sweden) received a median of 4 (range 1-19) pemetrexed maintenance cycles. Adherence rate up to Cycle 6 was 98.0% (95% confidence interval [CI]: 86.4%, 99.7%). All but 2 patients remained on HD. 1 patient discontinued after Cycle 1 (patient decision), and 1 after Cycle 6 (noncompliance with oral dexamethasone). 87% (33/38) of the patients preferred home to hospital treatment and in 90% (28/31) of cases, physicians were satisfied with distant management of patients. During HD Cycles 2-4 mean change from baseline ranged from 3.0 to 7.7 for EQ-5D visual analog scale. The 6-month OS rate was 73% (95% CI: 58%, 83%). 1 patient had an HD-related adverse event (device-related infection, Grade 2) and 1 patient died after Cycle 1, before HD, due to a possibly drug-related atypical pneumonia. Conclusion: HD of pemetrexed maintenance treatment in patients with advanced nsqNSCLC was feasible, safe, and preferred by patients, while maintaining HRQoL. Physicians were satisfied with distant patient management. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 8.
    Lal, Rohit
    et al.
    Guys and St Thomas Fdn Trust, England .
    Bourayou, Nawel
    Eli Lilly and Co, France .
    Hillerdal, Gunnar
    Karolinska University of Sjukhuset, Sweden .
    Nicolson, Marianne
    Aberdeen Royal Infirm, Scotland .
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Lorenzo, Maria
    Eli Lilly and Co, England .
    Dyachkova, Yulia
    Eli Lilly GmbH, Austria .
    Barriga, Susana
    Eli Lilly, Spain .
    Visseren-Grul, Carla
    Eli Lilly and Co, Netherlands .
    Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design2013In: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 11, no 163Article in journal (Refereed)
    Abstract [en]

    Background

    Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting.

    Methods

    Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0–1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m2 every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients’ quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011.

    Discussion

    This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home-based chemotherapy. The study design requires unusual methodology and specific logistics to address outcomes relevant to the home-delivery approach. This article presents a study design that offers a novel and reproducible model for home-based chemotherapy, and provides an up-to-date overview of the literature regarding this type of treatment.

  • 9.
    Rittmeyer, Achim
    et al.
    Lungenfachklin Immenhausen, Germany .
    Gorbunova, Vera
    NN Blokhin Cancer Research Centre Russia, Russia .
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Scherpereel, Arnaud
    CHRU Lille, France .
    Kim, Joo-Hang
    Yonsei University, South Korea .
    Ahn, Myung-Ju
    Sungkyunkwan University, South Korea .
    Chella, Antonio
    University of Pisa, Italy .
    Chouaid, Christos
    Hop St Antoine, France .
    Campbell, Alicyn K.
    Genentech Inc, CA USA .
    Barlesi, Fabrice
    Aix Marseille University, France .
    Health-Related Quality of Life in Patients with Advanced Nonsquamous Non-Small-Cell Lung Cancer Receiving Bevacizumab or Bevacizumab-Plus-Pemetrexed Maintenance Therapy in AVAPERL (MO22089)2013In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 8, no 11, p. 1409-1416Article in journal (Refereed)
    Abstract [en]

    Introduction: In the phase III AVAPERL trial, patients with advanced nonsquamous non-small-cell lung cancer receiving bevacizumab-plus-pemetrexed maintenance after first-line induction had a significant progression-free survival benefit relative to those treated with single-agent bevacizumab maintenance but with an increase in grade 3 adverse events. Here, we compare health-related quality of life (HRQOL) between AVAPERL maintenance arms. less thanbrgreater than less thanbrgreater thanMethods: Patient-reported outcomes were collected at designated intervals from preinduction to final visits. HRQOL was assessed using the self-administered European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Quality of Life Lung Cancer-Specific Module 13. Differences in scores of 10 points or more between arms were above the minimum important difference threshold and considered clinically meaningful. less thanbrgreater than less thanbrgreater thanResults: During induction, patient-reported coughing symptoms improved slightly, whereas fatigue and appetite loss scores worsened relative to preinduction baseline. During maintenance, changes in mean global health status and the majority of Quality of Life Questionnaire Core 30 and Quality of Life Lung Cancer-Specific Module 13 subscale scores did not differ between trial arms by the minimum important difference defining clinically meaningful (better or worse) patient-reported outcomes. Exceptions were patient-reported role functional status, fatigue symptoms and appetite loss symptoms (favoring bevacizumab), and pain in arm or shoulder symptoms (favoring bevacizumab-plus-pemetrexed maintenance), which differed by clinically meaningful amounts at more than one maintenance assessment. less thanbrgreater than less thanbrgreater thanConclusions: In AVAPERL, HRQOL remained relatively stable throughout maintenance and was generally similar in both arms. Despite an increase in adverse event rates, the addition of pemetrexed to bevacizumab maintenance resulted in similar stabilization of disease symptoms with improved efficacy outcomes.

  • 10.
    Schmekel, Birgitta
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Winquist, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Analysis of breath samples for lung cancer survival2014In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 840, p. 82-86Article in journal (Refereed)
    Abstract [en]

    Analyses of exhaled air by means of electronic noses offer a large diagnostic potential. Such analyses are non-invasive; samples can also be easily obtained from severely ill patients and repeated within short intervals. Lung cancer is the most deadly malignant tumor worldwide, and monitoring of lung cancer progression is of great importance and may help to decide best therapy. In this report, twenty-two patients with diagnosed lung cancer and ten healthy volunteers were studied using breath samples collected several times at certain intervals and analysed by an electronic nose. The samples were divided into three sub-groups; group d for survivor less than one year, group s for survivor more than a year and group h for the healthy volunteers. Prediction models based on partial least square and artificial neural nets could not classify the collected groups d, s and h, but separated well group d from group h. Using artificial neural net, group d could be separated from group s. Excellent predictions and stable models of survival day for group d were obtained, both based on partial least square and artificial neural nets, with correlation coefficients 0.981 and 0.985, respectively. Finally, the importance of consecutive measurements was shown.

  • 11.
    Svedberg, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, SE-58758 Linkoping, Sweden; KTH Royal Institute Technology, Sweden.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Lundeberg, Joakim
    KTH Royal Institute Technology, Sweden.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    A validated liquid chromatography tandem mass spectrometry method for quantification of erlotinib, OSI-420 and didesmethyl erlotinib and semi-quantification of erlotinib metabolites in human plasma2015In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 107, p. 186-195Article in journal (Refereed)
    Abstract [en]

    A liquid chromatography tandem mass spectrometry method was developed and validated for quantification of erlotinib and its metabolites in human plasma. The method is suitable for therapeutic drug monitoring and pharmacokinetic studies. The substances were extracted using protein precipitation, separated on a BEH XBridge C18 column (100 x 2.1 mm, 1.7 mu m) by gradient elution at 0.7 mL/min of acetonitrile and 5 mM ammonium acetate. The concentration was determined using a Waters Xevo triple quadrupole mass spectrometer in a multi reaction monitoring mode. The total run time was 7 min. Deuterated erlotinib and OSI-597 were used as internal standard for erlotinib and its metabolites, respectively. Erlotinib, OSI-420 and didesmethyl erlotinib were quantified in the concentration range 25-5000 ng/mL, 0.5-500 ng/mL and 0.15-10 ng/mL, respectively. Precision and accuracy was less than14% except for OSI-420 at LLOQ (17%). Extraction recovery was above 89%, 99% and 89% for erlotinib, OSI-420 and didesmethyl erlotinib, respectively. The human liver microsomes generated 14 metabolites, three of them not previously reported. Twelve metabolites were measured semi-quantitatively and validated with respect to selectivity, precision and stability. (C) 2014 Elsevier B.V. All rights reserved.

  • 12.
    Svedberg, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Hornstra, Niels
    Kalmar Cty Hosp, Sweden.
    Kentson, Magnus
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Branden, Eva
    Gavle Cent Hosp, Sweden; Uppsala Univ Reg Gavleborg, Sweden.
    Koyi, Hirsh
    Gavle Cent Hosp, Sweden; Uppsala Univ Reg Gavleborg, Sweden.
    Bergman, Bengt
    Univ Gothenburg, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Erlotinib treatment induces cytochrome P450 3A activity in non-small cell lung cancer patients2019In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 85, no 8, p. 1704-1709Article in journal (Refereed)
    Abstract [en]

    Aims Erlotinib is a tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer highly metabolized by the cytochrome P450 (CYP) 3A. Hence, CYP3A4 activity might be a useful predictor of erlotinib pharmacokinetics in personalized medicine. The effect of erlotinib on CYP3A activity was therefore studied in non-small cell lung cancer patients. Methods The study included 32 patients scheduled for erlotinib monotherapy. CYP3A activity was assessed using quinine as a probe before and during erlotinib treatment. Plasma from blood samples drawn 16 hours post quinine administration were analysed using HPLC with fluorescence detection to determine the quinine/3-OH-quinine ratio. Results Matched samples, available from 13 patients, showed an induction of CYP3A activity (P = 0.003, Wilcoxons signed rank test) after 2 months of treatment. The quinine/3-OH-quinine ratio decreased from 20.2 (+/- 13.4) at baseline to 11.0 (+/- 4.34). Single-point samples, available from 19 patients, supported the decrease in ratio (P = 0.007, Mann-Whitney U-test). Generally, females had a higher CYP3A activity both at baseline and after two months of treatment. Statistical analysis by gender also showed significant increase in CYP3A activity (males, n = 10, P = 0.001, and females, n = 22, P = 0.001). Conclusions An induction of CYP3A activity was observed after 2 months of erlotinib treatment which was also seen when subdividing based on gender. It could be important to take this into consideration for patients co-administering other CYP3A-metabolizing drugs during erlotinib treatment and also makes it difficult to use baseline CYP3A activity to predict erlotinib pharmacokinetics.

    The full text will be freely available from 2020-04-03 11:24
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