کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5528408 | 1547963 | 2017 | 5 صفحه PDF | دانلود رایگان |
- Treatment of MPM at progression after platinum-antifolate is an unmet need.
- The role of the FGFR pathway in MPM has not been fully elucidated.
- Dovitinib is a multi-targeted tyrosine kinase inhibitor of VEGFR and FGFR.
- In pre-treated MPM dovitinib had no significant activity and was poorly tolerated.
- It is unclear if at the doses administered FGFR was effectively inhibited.
ObjectivesFollowing failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM.MethodsThis open-label multicentre phase II trial [NCT01769547] enrolled fit, consenting adult patients with advanced MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy. Dovitinib was administered orally at 500Â mg/day for 5Â days on, 2Â days off, in 28-day cycles. Response was assessed every 2 cycles using RECIST 1.1 criteria modified for MPM. Correlative studies included FGFR-1 amplification on archival tumour and serum samples for circulating angiogenesis factors. The primary end-point was the proportion of patients progression-free at 3 months (PF3) using a two-stage design.Results12 patients (10 males, median age 67) were enrolled. The median number of cycles administered was 2.5 (range 1-8). One unconfirmed partial response was observed. PF3 was 50% (95% confidence interval 28.4% to 88.0%); although the criterion for proceeding to stage II accrual was met, the trial was halted due to a combination of minimal activity with several early progression events and poor tolerability in this patient population. One of 12 tumour specimens had low amplification of FGFR-1.ConclusionsDovitinib has minimal activity in previously-treated MPM. The role of the FGFR pathway in MPM remains unclear.
Journal: Lung Cancer - Volume 104, February 2017, Pages 65-69