scholarly journals Bilateral acute anterior uveitis: a rare ocular side effect of erlotinib

2019 ◽  
Vol 12 (12) ◽  
pp. e232868 ◽  
Author(s):  
Sarah Chan ◽  
Elizabeth Ahern ◽  
Sarah Chaudhry ◽  
Brett Hughes
Keyword(s):  
Anterior Uveitis ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Kinase Domain ◽  
Caucasian Woman ◽  
Acute Anterior Uveitis ◽  
Ocular Side ◽  
Epithelial Growth Factor ◽  
Post Marketing

Erlotinib used in the treatment of advanced non-small cell lung cancer (NSCLC) is a first-generation small-molecule tyrosine kinase inhibitor which reversibly inhibits the kinase domain of epithelial growth factor receptor (EGFR). The incidence of ocular toxicities as adverse effects (AE) of erlotinib is relatively common. However, post-marketing, acute anterior uveitis (AAU) has been reported in a small number of cases as a putative AE resulting from erlotinib therapy. We present a case of a 67-year-old, Caucasian woman, lifelong non-smoker with stage IV NSCLC who presents with decreased visual acuity and ‘floaters’ 6 weeks after commencing erlotinib. She was later diagnosed with erlotinib-associated bilateral AAU. This is the fifth documented case of erlotinib-associated bilateral AAU since 2010, highlighting the rarity of this AE. Thus, the possibility of AAU should always be considered in patients on EGFR-blocking therapies as significant ocular damage can occur if ophthalmic complaints are not triaged and assessed quickly.

scholarly journals Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush

2019 ◽  
Vol 12 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Nobuhiko Seki ◽  
Ryosuke Ochiai ◽  
Terunobu Haruyama ◽  
Masashi Ishihara ◽  
Maika Natsume ◽  
...  
Keyword(s):  
Substance P ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Subsequent Treatment ◽  
Treatment Schedule ◽  
Weekly Schedule ◽  
Patient Centered ◽  
Neurokinin 1 ◽  
Dermatological Side Effects

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.

Pharmacodynamic Studies of Gefitinib in Tumor Biopsy Specimens From Patients With Advanced Gastric Carcinoma

2006 ◽  
Vol 24 (26) ◽  
pp. 4309-4316 ◽  
Author(s):  
Federico Rojo ◽  
Josep Tabernero ◽  
Joan Albanell ◽  
Eric Van Cutsem ◽  
Atsushi Ohtsu ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Kinase Inhibitor ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Mitogen Activated Protein Kinase ◽  
Tumor Biopsy ◽  
Advanced Gastric Carcinoma ◽  
Egfr Expression ◽  
Phosphorylated Akt

Purpose Epidermal growth factor receptor (EGFR) is highly expressed in some gastric cancers and is implicated in cancer cell growth and proliferation. The objective of this study was to assess the in situ biologic activity of the EGFR tyrosine kinase inhibitor gefitinib in gastric tumor samples in a phase II study. Methods Patients with previously treated stage IV adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive gefitinib (250 or 500 mg/d). Tumor biopsies, obtained at screening and on day 28 of treatment, were assessed for biomarker expression using immunohistochemistry and analysis of apoptosis. Results One hundred sixteen tumor samples from 70 patients were available, 70 were baseline and 46 were on-therapy biopsies. At baseline, levels of EGFR expression significantly correlated with levels of phosphorylated EGFR (pEGFR; P < .001) and Ki67 expression (P = .011), but not with phosphorylated mitogen-activated protein kinase (pMAPK). After gefitinib treatment, levels of pEGFR in tumor cells were significantly reduced (P = .001); this was not the case for pMAPK and phosphorylated Akt (pAkt). However, in some cases gefitinib inhibited pAkt and these tumors had enhanced apoptosis. Likewise, there was a significant correlation between increased exposure to geftinib and enhanced apoptosis. Conclusion Gefitinib reached the tumors at concentrations sufficient to inhibit EGFR activation in advanced gastric carcinoma patients, although this did not translate into clinical benefit. Overall, intratumoral phosphorylation of MAPK and Akt was not significantly inhibited by gefitinib. However, the finding that decreases in pAkt correlated with enhanced apoptosis deserves further exploration.

ARG tyrosine kinase activity is inhibited by STI571

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2440-2448 ◽  
Author(s):  
Keiko Okuda ◽  
Ellen Weisberg ◽  
D. Gary Gilliland ◽  
James D. Griffin
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Fusion Partner ◽  
Induced Apoptosis

Abstract The tyrosine kinase inhibitor STI571 inhibits BCR/ABL and induces hematologic remission in most patients with chronic myeloid leukemia. In addition to BCR/ABL, STI571 also inhibits v-Abl, TEL/ABL, the native platelet-derived growth factor (PDGF)β receptor, and c-KIT, but it does not inhibit SRC family kinases, c-FMS, FLT3, the epidermal growth factor receptor, or multiple other tyrosine kinases. ARG is a widely expressed tyrosine kinase that shares substantial sequence identity with c-ABL in the kinase domain and cooperates with ABL to regulate neurulation in the developing mouse embryo. As described here, ARG has recently been implicated in the pathogenesis of leukemia as a fusion partner of TEL. A TEL/ARG fusion was constructed to determine whether ARG can be inhibited by STI571. When expressed in the factor-dependent murine hematopoietic cell line Ba/F3, the TEL/ARG protein was heavily phosphorylated on tyrosine, increased tyrosine phosphorylation of multiple cellular proteins, and induced factor-independent proliferation. The effects of STI571 on Ba/F3 cells transformed with BCR/ABL, TEL/ABL, TEL/PDGFβR, or TEL/ARG were then compared. STI571 inhibited tyrosine phosphorylation and cell growth of Ba/F3 cells expressing BCR/ABL, TEL/ABL, TEL/PDGFβR, and TEL/ARG with an IC50 of approximately 0.5 μM in each case, but it had no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by TEL/JAK2. Culture of TEL/ARG-transfected Ba/F3 cells with IL-3 completely prevented STI571-induced apoptosis in these cells, similar to what has been observed with BCR/ABL- or TEL/ABL-transformed cells. These results indicate that ARG is a target of the small molecule, tyrosine kinase inhibitor STI571.

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