Thalidomide consolidation improves progression-free survival in myeloma with normal but not up-regulated expression of fibroblast growth factor receptor 3: analysis from the Australasian Leukaemia and Lymphoma Group MM6 clinical trial

2012 ◽  
Vol 53 (9) ◽  
pp. 1728-1734 ◽  
Author(s):  
P. Joy Ho ◽  
Ross D. Brown ◽  
Andrew Spencer ◽  
Melinda Jeffels ◽  
Daniel Daniher ◽  
...  
2019 ◽  
Author(s):  
Eunhae Shin ◽  
Dong Hui Lim ◽  
Jisang Han ◽  
Do-Hyun Nam ◽  
Keunchil Park ◽  
...  

Abstract Background To describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis. Materials Retrospective chart review. Results Among 6,871 patients and 17 EGFR or FGFR inhibitors, 1,161 patients (16.9%) referred for ophthalmologic examination. Authors identified that in twelve patients, 3 EGFR inhibitors and 2 FGFR inhibitors that caused corneal epithelial lesions. Vandetanib, Osimertinib, and an EGFR agent under clinical trial (ABT-414) caused vortex keratopathy in nine patients and ASP5878 and FPA144, the FGFR inhibitors of clinical trial caused epithelial changes resembling corneal dysmaturation in three patients. Mean interval until symptoms appear was 246 days with Vandetanib, 196 days with Osimertinib, 30 days with ABT-414, 55 days with ASP5878 and 70 days with FPA144. Mean of lowest logarithm of minimal angle of resolution units (logMAR) visual acuity of right eye after chemotherapy was 0.338 and 0.413 in left eye. Incidence of epithelial changes were 15.79% with Vandetanib, 0.005% with Osimertinib, 100% with ABT414, 50.0% with ASP5878 and 18.2% with FPA144. After excluding deceased patients, or were lost to follow-up or were still undergoing treatment, we confirmed the reversibility of corneal lesions after discontinuation of each agent. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy. Conclusions EGFR and FGFR inhibitors are well known chemotherapy agents and could make corneal epithelial changes. Contrary to low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with EGFR or FGFR inhibitors that decreased visual acuity could develop due to corneal epithelial changes, and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops.


2019 ◽  
Author(s):  
Eunhae Shin ◽  
Dong Hui Lim ◽  
Jisang Han ◽  
Do-Hyun Nam ◽  
Keunchil Park ◽  
...  

Abstract Background To describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis. Materials Retrospective chart review. Results Among 6,871 patients and 17 EGFR or FGFR inhibitors, authors identified five EGFR inhibitors and two FGFR inhibitors that cause such corneal lesions. Unlike other old EGFR agents with rare ocular complications, Vandetanib, Osimertinib, and 3 EGFR agents under clinical trial (ABT-414, ASP5878, FPA144) caused vortex keratopathy in nine patients and ASP5878 and FPA144, the FGFR inhibitors of clinical trial caused epithelial changes resembling corneal dysmaturation in three patients. ABT-414 showed a remarkably short interval from the start of therapy to initiation of keratopathy. After excluding deceased patients, or were lost to follow-up or were still undergoing treatment, we confirmed the reversibility of corneal lesions after discontinuation of each agent. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy. Conclusions EGFR and FGFR inhibitors are well known chemotherapy agents and could make corneal epithelial changes. Contrary to low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with EGFR or FGFR inhibitors that decreased visual acuity could develop due to corneal epithelial changes, and also reassure them that the condition is reversible after the end of treatment without the use of steroid eye drops.


2014 ◽  
Vol 67 (12) ◽  
pp. 1056-1061 ◽  
Author(s):  
Chien-Feng Li ◽  
Hong-Lin He ◽  
Jaw-Yuan Wang ◽  
Hsuan-Ying Huang ◽  
Ting-Fe Wu ◽  
...  

AimsNeoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is an increasingly used therapeutic strategy for advanced rectal cancer, but risk stratification and final outcomes remain suboptimal. Recently, the oncogenic role of the fibroblast growth factor/fibroblast growth factor receptor (FGFR) signalling pathway has been recognised; however, its clinical significance in rectal cancer has not been elucidated. In this study, we identify and validate targetable drivers associated with the FGFR signalling pathway in rectal cancer patients treated with CCRT.MethodsUsing a published transcriptome of rectal cancers, we found FGFR2 gene significantly predicted response to CCRT. The expression levels of FGFR2, using immunohistochemistry assays, were further evaluated in 172 rectal cancer specimens that had not received any treatment. Expression levels of FGFR2 were statistically correlated with major clinicopathological features and clinical survival in this valid cohort.ResultsHigh expression of FGFR2 was significantly related to advanced pretreatment tumour (p=0.022) and nodal status (p=0.026), post-treatment tumour (p<0.001) and nodal status (p=0.004), and inferior tumour regression grade (p<0.001). In survival analyses, high expression of FGFR2 was significantly associated with shorter local recurrence-free survival (p=0.0001), metastasis-free survival (MeFS; p=0.0003) and disease-specific survival (DSS; p<0.0001). Notably, high expression of FGFR2 was independently predictive of worse outcomes for MeFS (p=0.002, HR=5.387) and DSS (p=0.004, HR=4.997).ConclusionsHigh expression of FGFR2 is correlated with advanced tumour stage, poor therapeutic response and worse survival in rectal cancer patients receiving neoadjuvant CCRT. These findings indicate that FGFR2 is a prognostic factor for treating rectal cancer.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1706
Author(s):  
Patrick C. Lee ◽  
Andrew Hendifar ◽  
Arsen Osipov ◽  
May Cho ◽  
Daneng Li ◽  
...  

Landmark molecular profiling efforts have identified multiple targetable alterations in cholangiocarcinoma. Among the molecular-driven subsets of cholangiocarcinoma, targeting the fibroblast growth factor receptor (FGFR) has shown promise and represents the first targeted therapy to be approved in treatment-refractory, advanced cholangiocarcinoma. In this review, we provide an up-to-date overview of the clinical development of FGFR inhibitors in advanced cholangiocarcinoma. We review the FGFR pathway and discuss emerging issues including resistance to FGFR inhibitors. We end with a discussion on future considerations to optimize the potential of this class of therapeutics in advanced cholangiocarcinoma.


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