Literature DB >> 26043707

MEK inhibitors: a new class of chemotherapeutic agents with ocular toxicity.

K E Duncan1, L Y Chang2, M Patronas1.   

Abstract

A new class of chemotherapeutic agents, MEK inhibitors, has recently been developed and is proving to be an effective treatment for a number of cancers. A pattern of ocular adverse events has followed these drugs through clinical trials and their association with retinopathy is only just beginning to be recognized. We present two cases of MEK inhibitor-associated retinopathy followed by a review of the current literature on ocular toxicity associated with MEK inhibitors. Patients undergoing treatment with MEK inhibitors appear to have high rates of multifocal serous retinal detachments as well as retinal vein occlusions. We present the first report of cystoid macular edema associated with MEK inhibitor use. The mechanism of these adverse events is still unclear though they seem to be related to oxidative stress and blood retinal barrier breakdown. Management of the ocular toxicity can range from observation to topical treatments or intravitreal injections. Fortunately most ocular adverse events appear to be self-limited and do not require discontinuing the MEK inhibitor. Discontinuation or decreased dosing of MEK inhibitors may be reserved for cases of severe sight-threatening ocular toxicity.

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Year:  2015        PMID: 26043707      PMCID: PMC4541356          DOI: 10.1038/eye.2015.82

Source DB:  PubMed          Journal:  Eye (Lond)        ISSN: 0950-222X            Impact factor:   3.775


  22 in total

1.  Improved survival with MEK inhibition in BRAF-mutated melanoma.

Authors:  Keith T Flaherty; Caroline Robert; Peter Hersey; Paul Nathan; Claus Garbe; Mohammed Milhem; Lev V Demidov; Jessica C Hassel; Piotr Rutkowski; Peter Mohr; Reinhard Dummer; Uwe Trefzer; James M G Larkin; Jochen Utikal; Brigitte Dreno; Marta Nyakas; Mark R Middleton; Jürgen C Becker; Michelle Casey; Laurie J Sherman; Frank S Wu; Daniele Ouellet; Anne-Marie Martin; Kiran Patel; Dirk Schadendorf
Journal:  N Engl J Med       Date:  2012-06-04       Impact factor: 91.245

Review 2.  Clinical experience of MEK inhibitors in cancer therapy.

Authors:  Ding Wang; Scott A Boerner; James D Winkler; Patricia M LoRusso
Journal:  Biochim Biophys Acta       Date:  2006-11-16

3.  Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies.

Authors:  Patricia M Lorusso; Alex A Adjei; Mary Varterasian; Shirish Gadgeel; Joel Reid; David Y Mitchell; Lorelei Hanson; Pamela DeLuca; Laura Bruzek; Jill Piens; Peggy Asbury; Keri Van Becelaere; Roman Herrera; Judith Sebolt-Leopold; Mark B Meyer
Journal:  J Clin Oncol       Date:  2005-07-11       Impact factor: 44.544

4.  Transient MEK inhibitor-associated retinopathy in metastatic melanoma.

Authors:  U Urner-Bloch; M Urner; P Stieger; N Galliker; N Winterton; A Zubel; L Moutouh-de Parseval; R Dummer; S M Goldinger
Journal:  Ann Oncol       Date:  2014-05-26       Impact factor: 32.976

5.  Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers.

Authors:  Patricia M LoRusso; Smitha S Krishnamurthi; John J Rinehart; Lisle M Nabell; Lisa Malburg; Paul B Chapman; Samuel E DePrimo; Steven Bentivegna; Keith D Wilner; Weiwei Tan; Alejandro D Ricart
Journal:  Clin Cancer Res       Date:  2010-03-09       Impact factor: 12.531

6.  First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors.

Authors:  Maria Martinez-Garcia; Udai Banerji; Joan Albanell; Rastilav Bahleda; Saoirse Dolly; Françoise Kraeber-Bodéré; Federico Rojo; Emilie Routier; Ernesto Guarin; Zhi-Xin Xu; Ruediger Rueger; Jean J L Tessier; Eliezer Shochat; Steve Blotner; Valerie Meresse Naegelen; Jean-Charles Soria
Journal:  Clin Cancer Res       Date:  2012-07-03       Impact factor: 12.531

7.  Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer.

Authors:  John Rinehart; Alex A Adjei; Patricia M Lorusso; David Waterhouse; J Randolph Hecht; Ronald B Natale; Oday Hamid; Mary Varterasian; Peggy Asbury; Eric P Kaldjian; Stephen Gulyas; David Y Mitchell; Roman Herrera; Judith S Sebolt-Leopold; Mark B Meyer
Journal:  J Clin Oncol       Date:  2004-10-13       Impact factor: 44.544

8.  Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers.

Authors:  Alex A Adjei; Roger B Cohen; Wilbur Franklin; Clive Morris; David Wilson; Julian R Molina; Lorelei J Hanson; Lia Gore; Laura Chow; Stephen Leong; Lara Maloney; Gilad Gordon; Heidi Simmons; Allison Marlow; Kevin Litwiler; Suzy Brown; Gregory Poch; Katie Kane; Jerry Haney; S Gail Eckhardt
Journal:  J Clin Oncol       Date:  2008-04-07       Impact factor: 44.544

9.  Mutations of the BRAF gene in human cancer.

Authors:  Helen Davies; Graham R Bignell; Charles Cox; Philip Stephens; Sarah Edkins; Sheila Clegg; Jon Teague; Hayley Woffendin; Mathew J Garnett; William Bottomley; Neil Davis; Ed Dicks; Rebecca Ewing; Yvonne Floyd; Kristian Gray; Sarah Hall; Rachel Hawes; Jaime Hughes; Vivian Kosmidou; Andrew Menzies; Catherine Mould; Adrian Parker; Claire Stevens; Stephen Watt; Steven Hooper; Rebecca Wilson; Hiran Jayatilake; Barry A Gusterson; Colin Cooper; Janet Shipley; Darren Hargrave; Katherine Pritchard-Jones; Norman Maitland; Georgia Chenevix-Trench; Gregory J Riggins; Darell D Bigner; Giuseppe Palmieri; Antonio Cossu; Adrienne Flanagan; Andrew Nicholson; Judy W C Ho; Suet Y Leung; Siu T Yuen; Barbara L Weber; Hilliard F Seigler; Timothy L Darrow; Hugh Paterson; Richard Marais; Christopher J Marshall; Richard Wooster; Michael R Stratton; P Andrew Futreal
Journal:  Nature       Date:  2002-06-09       Impact factor: 49.962

10.  Bilateral Multifocal Central Serous-Like Chorioretinopathy due to MEK Inhibition for Metastatic Cutaneous Melanoma.

Authors:  Scott D Schoenberger; Stephen J Kim
Journal:  Case Rep Ophthalmol Med       Date:  2013-03-11
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  25 in total

1.  MEK inhibitors: a new class of chemotherapeutic agents with ocular toxicity.

Authors:  L Maubon; N Hirji; R Petrarca; P Ursell
Journal:  Eye (Lond)       Date:  2015-11-20       Impact factor: 3.775

2.  Ocular Toxicity Profile of ST-162 and ST-168 as Novel Bifunctional MEK/PI3K Inhibitors.

Authors:  Andrew Smith; Mercy Pawar; Marcian E Van Dort; Stefanie Galbán; Amanda R Welton; Greg M Thurber; Brian D Ross; Cagri G Besirli
Journal:  J Ocul Pharmacol Ther       Date:  2018-04-30       Impact factor: 2.671

3.  Phase I trial of MEK 1/2 inhibitor pimasertib combined with mTOR inhibitor temsirolimus in patients with advanced solid tumors.

Authors:  Monica Mita; Siqing Fu; Sarina Anne Piha-Paul; Filip Janku; Alain Mita; Ronald Natale; Wei Guo; Charles Zhao; Razelle Kurzrock; Aung Naing
Journal:  Invest New Drugs       Date:  2017-02-13       Impact factor: 3.850

4.  Separation of outer retinal layers secondary to selumetinib.

Authors:  Robert A Avery; Carmelina Trimboli-Heidler; Lindsay B Kilburn
Journal:  J AAPOS       Date:  2016-04-21       Impact factor: 1.220

5.  Clinical and Morphologic Characteristics of MEK Inhibitor-Associated Retinopathy: Differences from Central Serous Chorioretinopathy.

Authors:  Jasmine H Francis; Larissa A Habib; David H Abramson; Lawrence A Yannuzzi; Murk Heinemann; Mrinal M Gounder; Rachel N Grisham; Michael A Postow; Alexander N Shoushtari; Ping Chi; Neil H Segal; Rona Yaeger; Alan L Ho; Paul B Chapman; Federica Catalanotti
Journal:  Ophthalmology       Date:  2017-07-12       Impact factor: 12.079

6.  [Paraneoplastic serous retinopathies: hormones, mediators, and inhibitors].

Authors:  R S Grajewski; L M Heindl
Journal:  Ophthalmologe       Date:  2017-04       Impact factor: 1.059

Review 7.  Ocular Toxicity of Tyrosine Kinase Inhibitors.

Authors:  Mary Elizabeth Davis
Journal:  Oncol Nurs Forum       Date:  2016-03       Impact factor: 2.172

8.  FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.

Authors:  Akosua A Nti; Leona W Serrano; Harpal S Sandhu; Katherine E Uyhazi; Ilaina D Edelstein; Elaine J Zhou; Scott Bowman; Delu Song; Tara C Gangadhar; Lynn M Schuchter; Sheryl Mitnick; Alexander Huang; Charles W Nichols; Ravi K Amaravadi; Benjamin J Kim; Tomas S Aleman
Journal:  Retina       Date:  2019-03       Impact factor: 4.256

Review 9.  Neuro-ophthalmic side effects of molecularly targeted cancer drugs.

Authors:  M T Bhatti; A K S Salama
Journal:  Eye (Lond)       Date:  2017-10-20       Impact factor: 3.775

Review 10.  MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road.

Authors:  Christopher J Caunt; Matthew J Sale; Paul D Smith; Simon J Cook
Journal:  Nat Rev Cancer       Date:  2015-10       Impact factor: 60.716

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