Risk Factors for Eye Disorders Caused by Paclitaxel: A Retrospective Study

Abstract

Paclitaxel and nanoparticle albumin-bound paclitaxel are known to cause adverse events of eye disorders, such as cystoid macular edema. However, at present, the risk factors remain unclear. Therefore, risk factors for eye disorders caused by paclitaxel and nanoparticle albumin-bound paclitaxel were studied. This retrospective study targeted patients who were newly administered paclitaxel or nanoparticle albumin-bound paclitaxel at Kyoto Okamoto Memorial Hospital between April 1, 2012, and March 31, 2017. Eye disorder occurrence was defined as an event in which the pharmacist confirmed the symptoms in a patient interview and the ophthalmologist diagnosed the disorder. To analyze the risk factors, logistic regression analysis using 41 factors was performed. Of 128 subjects, 13 (10.2%) had eye disorders with symptom degrees of Grades 1 and 2. The symptoms were conjunctivitis or subconjunctival hemorrhage (3.1%), visual acuity reduction (2.3%), blurred vision and eye pain (1.6% each), eye mucus, blepharitis, stye, watering eyes, photopsia, and muscae volitantes (0.8% each). In eight patients, the conditions patients improved with spontaneously or with medication use; no improvements were observed the cases of visual acuity reduction, blurred vision, or muscae volitantes. Multivariate logistic regression analysis revealed that a cumulative dose of ≥819 mg/m 2 (odds ratio: 5.34, 95% confidence interval: 1.32-21.60, p 0.019) and baseline alkaline phosphatase ≥256 U/L (odds ratio: 3.74, 95% confidence interval: 1.02-13.70, p 0.046) were significant risk factors associated with eye disorders. In conclusion, it was determined that paclitaxel-and nanoparticle albumin-bound paclitaxelrelated eye disorders might be influenced by cumulative dose and baseline alkaline phosphatase.

Current status of eye disorders caused by docetaxel administration every 3 weeks: A case-control study in Japanese patients

“…We previously reported that visual acuity reduction caused by PTX occurred in 2.3% of patients, and no cases of cystoid macular edema were noted. 5 No cases of cystoid macular edema were noted even in the present study. However, visual acuity reduction or blurred vision may be an early symptom of cystoid macular edema.…”

“…The evaluation of adverse events was performed as follows: (1) Pharmacists asked the patient about the occurrence of general adverse events; (2) For typical adverse events, such as nausea and edema, pharmacists confirmed the presence or absence of the symptoms and severity of the symptoms by closed questions; (3) For other adverse events, pharmacists confirmed by open questions, such as ''Have you experienced a change in your physical condition? ''; (4) If patients complained about eye disorders, pharmacists confirmed the time of onset of symptoms and details of symptoms; (5) Pharmacists reported to the doctor and requested the doctor to consult with the ophthalmologist or pharmacists advised patients to undergo an ophthalmology consultation; and (6) The ophthalmologist diagnosed eye disorders.…”

“…Since July 2009 at the Kyoto Okamoto Memorial Hospital, pharmacists have been monitoring adverse events for all patients who had undergone chemotherapy in the outpatient chemotherapy room; moreover, we have previously reported that eye disorders are associated with the use of paclitaxel (PTX), capecitabine, oxaliplatin, docetaxel (DTX), and cabazitaxel. [3][4][5][6][7][8][9] DTX is an antineoplastic agent used for the treatment of many types of cancer, such as breast, lung, and gastric cancers. Common adverse events of DTX include bone marrow suppression, edema, and skin disorders.…”

Impact of Cryotherapy on Sensory, Motor, and Autonomic Neuropathy in Breast Cancer Patients Receiving Paclitaxel: A Randomized, Controlled Trial

“…One study found the association between cryotherapy and lower CIPN20 autonomic scores, although they concluded that clinical relevance was unlikely (19). Autonomic symptoms were infrequently reported and rarely considered cardinal adverse effects of paclitaxel (36,37). Potentially, the observed improvement in SSR and CIPN20 autonomic subscale could be the inherent effect of cryotherapy, regardless of chemotherapy.…”

Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors

“…Alkylating agent/platinum Blurred vision, retinotoxicity (retinal ischaemia and neovascularization), optic neuropathy [33] Doxorubicin anthracyline drug conjunctivitis (m/c), periorbital edema, lacrimation, blepharospasm, keratitis, and decreased visual acuity [34] Everolimus mTOR inhibitor posterior reversible encephalopathy syndrome,bilateral optic neuropathy [35] Geftinib EGFR-inhibitor Dry eye, corneal ulcer [36,37] Gemcitabine antimetabolite agent uveal effusion and outer retinal disruption or Purtscher-like retinopathy with combination of docetaxel [25,38] Irinotecan topoisomerase I inhibitor None [39], none in combination regimen with 5-fluorouracil, oxaliplatin and bevacizumab [40] Oxaliplatin platinum dry eye, lacrimation, conjunctivitis, damage of the retinal pigment epithelium and the optic nerve, visual field defect [30,41] Paclitaxel Antimicrotubule agent epiphora, eye pain, conjunctivitis, blepharitis, blurred vision [24,42] Pemetrexed Antimetabolite /antifolate AION [1], eyelid edema [24,43] Ramucirumab monoclonal Ab of VEGFR-2 none [28] Sorafenib anti-VEGF agent blurred vision, periocular edema, retinal detachment, ptosis, optic neuropathy, macular edema [27,44] Temozolomide alkylating/methylating agent blurred vision with concurrent radiation therapy [45].…”