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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
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
Vise andre og tillknytning
2013 (engelsk)Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 1, s. 115-120Artikkel i tidsskrift (Fagfellevurdert) 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.

Methods:

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.

Results:

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).

Conclusion:

Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.

sted, utgiver, år, opplag, sider
2013. Vol. 49, nr 1, s. 115-120
Emneord [en]
Celecoxib, Chemotherapy, Non-small cell lung cancer, Plasma VEGF, Survival
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-191988DOI: 10.1016/j.ejca.2012.07.032ISI: 000312896700015OAI: oai:DiVA.org:uu-191988DiVA, id: diva2:600498
Tilgjengelig fra: 2013-01-24 Laget: 2013-01-15 Sist oppdatert: 2017-12-06bibliografisk kontrollert

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