Discussion
ocular toxicity, toxicity, toxicities, uveitis, ocular toxicities
DRY EYE, DIM VISION, UVEITIS
This study examined 37 ocular toxicities in 33 patients treated with investigational drugs in early phase clinical trials conducted in the NCCH. A high incidence of ocular toxicities was observed following treatment with HSP90 inhibitors and FGFR inhibitors. Some ocular toxicities arose after a long period of time from the initial administration of the drug. Most patients developed ocular toxicities even though their dose was below the MTD. Ocular toxicities were generally not severe and were reversible after a temporary hold of the drug. Bilateral ocular toxicity could be used as a trigger for diagnosis of drug-induced toxicities.Four patients had unique ocular toxicities with only subjective symptoms, lacking objective findings. For example, patients with dim vision related to an HSP-90 inhibitor experienced subjective symptoms such as seeing darker images, as if the lights were off even in bright places. Not all patients showed electroretinography changes, probably because damage to the outer retinal layer related to the HSP-90 inhibitor was minimal. There were 12 patients without subjective symptoms and showing only objective findings. Their ocular toxicities were detected by objective findings prior to the onset of subjective symptoms. Hence, we were able to start the treatment early and to prevent toxicities from becoming serious. In future early phase clinical trials, ophthalmologic examinations should be carefully considered after toxicity studies in vivo.Some differences between previous clinical trials in the types and frequencies of ocular toxicities were observed. While dry eye and uveitis are reportedly common ocular toxicities associated with ICIs [The specific patient group, which only included those involved in early clinical trials, is a limitation. Further, the detailed mechanisms of the toxicities are still unknown. In the late phase trials with more patients joined, careful watching on the severity and the timing of onset of ocular toxicities, depending on each type of drug, is needed.