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Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy
Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.ORCID iD: 0000-0002-8365-3132
Uppsala University, Sweden .
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2013 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 1, 115-120 p.Article in journal (Refereed) Published
Abstract [en]

Aim of the study: The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo. less thanbrgreater than less thanbrgreater thanMethods: In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks. less thanbrgreater than less thanbrgreater thanResults: VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028). less thanbrgreater than less thanbrgreater thanConclusion: Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.

Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 49, no 1, 115-120 p.
Keyword [en]
Non-small cell lung cancer, Celecoxib, Chemotherapy, Survival, Plasma VEGF
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-88362DOI: 10.1016/j.ejca.2012.07.032ISI: 000312896700015OAI: oai:DiVA.org:liu-88362DiVA: diva2:602881
Note

Funding Agencies|Ostergotland County Council, Medical Research Council of South-East Sweden (FORSS)||

Available from: 2013-02-04 Created: 2013-02-04 Last updated: 2017-12-06

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Sörenson, SverreFohlin, HelenaLindgren, AndreaSederholm, ChristerClinchy, Birgitta
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Pulmonary MedicineFaculty of Health SciencesDepartment of Respiratory MedicineAllergy CenterDepartment of Clinical and Experimental MedicineRegional Cancer Center South East SwedenInternal Medicine
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