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ABSTRACT: Background
Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated.Patients and methods
Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800?mg per day per os) was administered until progressive disease (PD). Circulating tumour cells (CTCs) were enumerated using the Cellsearch assay.Results
All patients were evaluable for response and toxicity. In the intention-to-treat analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence interval (CI): 5.0-22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD. Accrual in cohort B was halted because the hard-stop rule was met; in cohort A, the PFS-R was 59% (95% CI: 43.5-74.4; PR=7, SD=16). Nine (23.1%) patients received pazopanib for >6 months and 3 of them for >12 months. One pazopanib cycle resulted to a significant decrease to the number of patients with ?5 CTCs/7.5?ml of blood (20%) compared with baseline (50%). The median PFS and OS for all patients was 2.5 months (95% CI: 1.9-3.1 months) and 6.0 months (95% CI: 3.8-8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No unexpected toxicity was observed.Conclusions
Second-line treatment with pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising objective responses and disease control; CTC enumeration might serve as a reliable surrogate biomarker of response.
SUBMITTER: Koinis F
PROVIDER: S-EPMC5520202 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Koinis F F Agelaki S S Karavassilis V V Kentepozidis N N Samantas E E Peroukidis S S Katsaounis P P Hartabilas E E Varthalitis I I II Messaritakis I I Fountzilas G G Georgoulias V V Kotsakis A A
British journal of cancer 20170516 1
<h4>Background</h4>Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated.<h4>Patients and methods</h4>Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival ...[more]