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

PURPOSE: Docetaxel is known to cause eye disorders. In this study, current status of eye disorders caused by docetaxel administration every 3 weeks in Japanese patients was examined. METHODS: This case-control study targeted patients who were newly administered docetaxel at the Kyoto Okamoto Memorial Hospital between 1 July 2015 and 30 June 2018. 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. RESULTS: Of the 89 subjects, 7 (7.9%) had eye disorders. The symptoms were watering eyes (7.9%), a stye and eye discharge (2.2% each), corneal and conjunctival disorder, visual acuity reduction, and blepharedema (1.1% each). Four patients who presented with watering eyes, eye discharge, or corneal and conjunctival disorder showed improvement with the use of eye drops such as artificial tears. Two patients who presented with a stye showed improvement with the use of oral cefcapene. One patient with mild symptoms showed spontaneous improvement. However, one patient had irreversible visual acuity reduction. The multivariate logistic regression analysis revealed that a cumulative docetaxel dose of ≥300 mg/m2 (odds ratio: 15.50, 95% confidence interval: 1.37-175.00, p = 0.027) and concomitant cyclophosphamide use (odds ratio: 13.20, 95% confidence interval: 1.13-153.00, p = 0.039) were significant risk factors associated with eye disorders. CONCLUSION: In conclusion, it was determined that docetaxel-related eye disorders might be influenced by the cumulative dose of docetaxel and concomitant cyclophosphamide use. In addition, relatively mild symptoms improved with medication.

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

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/m2 (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 paclitaxel-related eye disorders might be influenced by cumulative dose and baseline alkaline phosphatase.

[An Undeniable Case of Optic Neuropathy Due to Cabazitaxel].

Cabazitaxelis a taxane-type antineoplastic agent used for treating prostate cancer. Although typical side effects include neutropenia and fatigue, no studies have investigated eye disorders as a possible side effect, and the details are not clear. Herein, we report our experience of an undeniable case of optic neuropathy caused by cabazitaxel. A 78-year-old man had been diagnosed with prostate cancer (cT3aN1M1b, stage IV) 3 years previously, with a treatment history of bicalutamide, leuprorelin, flutamide, docetaxel, abiraterone, and enzalutamide. Because of a decline in vision during the second and third administration cycles of cabazitaxel, the patient visited an ophthalmologist. He was found to have reduced visual acuity, reduced central critical flicker frequency, narrowed field of vision, and impaired color vision, and was diagnosed with optic neuropathy. Although cabazitaxel administration was continued through 6 cycles, the symptoms were unchanged, and no drastic exacerbation was seen. This patient undeniably developed optic neuropathy due to cabazitaxel. Optic neuropathy due to taxane-type antineoplastic agents has also been reported with paclitaxel or docetaxel, and all precautions should be taken when administering such drugs. Detailed studies that include data from a larger number of facilities should be conducted in the future.

[A Retrospective Analysis of Epiphora Due to Docetaxel].

Docetaxel is an antineoplastic agent used to treat breast cancer and several other types of cancer. Typical adverse drug reactions with docetaxel include myelosuppression and edema, but there have also been numerous reports of eye disorders, such as epiphora and lacrimal duct obstruction. Reports from Japan on such reactions, however, are limited; the duration and frequency of their appearance and other factors have not been elucidated. Since this information would be useful in routine medical practice, we conducted a retrospective analysis of epiphora due to docetaxel. Of the 48 breast cancer patients who commenced new 3-weekly docetaxel dosage regimens during the study period, 6 (12.5%) presented with epiphora. The patients with epiphora were receiving docetaxel at a significantly greater dose intensity (mg/m 2/3 weeks) than those in whom epiphora did not present (72.7 vs 67.1, p=0.0427). The timing of the reaction had no fixed pattern, and the symptoms were reversible in all cases, recorded as Grade 1 or 2. Thus, epiphora due to docetaxel during a 3-weekly dosage regimen presented rather frequently in Japanese patients, and the symptoms were reversible and mild. We found that greater dose intensity might be a risk factor for epiphora. More detailed studies that include data from a large number of facilities should be conducted in the future.

[A case of lacrimal duct obstruction caused by capecitabine].

In recent years, the incidence of adverse ocular reactions, including corneal problems and lacrimal duct obstruction, due to antineoplastic agents such as S-1 has increased. Very few reports of adverse ocular reactions caused by capecitabine, a fluorinated pyrimidine antineoplastic agent like S-1, exist, and consequently, the mechanism underlying these reactions is not well understood. This report describes our recent experience with a case of lacrimal duct obstruction caused by capecitabine. The patient was a 71-year-old woman who was being administered trastuzumab plus capecitabine combination chemotherapy for breast cancer-related bone metastasis. She complained of epiphora 7 days after capecitabine was initiated. Thereafter, her capecitabine dose was reduced owing to exacerbation of hand-foot syndrome, but the epiphora persisted. Capecitabine was discontinued 287 days after initiation owing to exacerbation of the hand-foot syndrome. However, because the epiphora persisted, the patient visited the ophthalmology department. The ophthalmologist diagnosed the patient with binocular nasolacrimal duct obstruction and cataract, and prescribed a 0.3% gatifloxacin ophthalmic solution and 0.1% fluorometholone ophthalmic suspension. Thereafter, the epiphora reduced. When the patient returned to the ophthalmology department, symptom improvement was confirmed. In this case, lacrimal duct obstruction likely developed due to capecitabine. The symptoms were reversible with discontinuation of capecitabine and ophthalmic treatment. We believe that reporting this case could be valuable in discussing capecitabine-induced lacrimal duct obstruction.

[A Retrospective Analysis of Eye Disorders Due to Oxaliplatin].

In recent years, the incidence of eye disorders due to antineoplastic agents such as S-1 has increased. Eye disorders including visual field defect, visual field impairment, optic neuritis, and visual acuity reduction have been reported as serious adverse effects of oxaliplatin, an agent that is frequently used as a standard therapy for colorectal cancer. However, specific details about these conditions, such as the timing relative to oxaliplatin administration and frequencies at which they appear, remain to be clarified; therefore, we conducted a retrospective analysis of patients with eye disorders due to oxaliplatin in order to obtain evidence that would be useful in routine medical practice. Of the 55 patients who were treated with oxaliplatin in this analysis 10 (18.2%) presented with eye disorders, including blepharoptosis (5 patients, 9.1%), visual field impairment (2 patients, 3.6%), visual acuity reduction (2 patients, 3.6%), eye pain (1 patient, 1.8%), congestion (1 patient, 1.8%), watering eyes (1 patient, 1.8%), and blurred vision (1 patient, 1.8%). These symptoms appeared during the early period of treatment, such as after the first or the second dose. We found that all patients had mild symptoms (Grade 1 or 2), and most improved spontaneously. Thus, eye disorders due to oxaliplatin affect Japanese patients somewhat frequently, although the symptoms are reversible and are mild in most cases. Detailed studies that include data from a larger number of facilities should be conducted in the future.

[Survey of the current status of capecitabine-induced hypertriglyceridemia].

We encountered cases of capecitabine-induced increase in blood triglyceride (TG) levels, which is relatively rare in routine medical practice. Although capecitabine-induced hypertriglyceridemia (CI-HTG) has been occasionally reported in other countries, such cases have not been reported in Japan. Therefore, the details of this condition remain to be clarified. To obtain evidence that would be useful in routine medical practice, we conducted a retrospective study of patients with CI-HTG. The study included 56 patients, of whom, 14 (25.0%) had TG levels < 150 mg/dL before capecitabine treatment that increased to ≥ 150 mg/dL after treatment. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v4.0, Japanese edition, Japan Clinical Oncology Group version (CTCAE v4.0-JCOG). We found that TG levels were markedly elevated (≥ Grade 3) in 2 patients (3.6%). Thus, CI-HTG also affects Japanese patients, although its frequency is relatively low. Detailed studies including a larger number of facilities should be conducted in future.

[Survey of current status of adverse ocular reactions to paclitaxel and a retrospective analysis for aiding in early detection of adverse reactions].

We have observed several cases of adverse reactions to paclitaxel, including visual impairment and lacrimation. Therefore, we conducted a survey of the current status of adverse reactions to paclitaxel and also performed a retrospective analysis of the initial symptoms and the times of their appearance. Of the 22 study patients, 8(36. 4%)presented with adverse ocular reactions, such as visual impairment and lacrimation, and for 3(13. 6%), an ophthalmologist confirmed that paclitaxel could not be ruled out as the direct cause of their adverse reactions. The group of patients who presented with adverse ocular reactions included significantly more patients with ocular complications and a previous history of ocular ailments, compared to the group showing no such reactions. The timing of reaction appearance did not show a consistent pattern. The results of this study suggest that the initial symptoms were mainly visual impairment and lacrimation, and that caution must be taken when administering paclitaxel to patients with a previous history of ocular ailments and ocular complications because of the risk of adverse ocular reactions. Thus, adverse ocular reactions to paclitaxel were indicated as a possible risk, in addition to other adverse events such as myelosuppression and peripheral neuropathy.

[Role of pharmacists in cardiopulmonary resuscitation (CPR)].

In January 2007, Daini Okamoto General Hospital introduced a new system in which pharmacists, together with physicians and nurses, address patients with cardiopulmonary arrest on arrival and inpatients with de novo cardiopulmonary arrest. Over the past 2 years since the introduction of the system, the role of pharmacists in cardiopulmonary resuscitation (CPR) at the hospital has become increasingly established. Pharmacists prepare drugs for CPR, measure intervals during drug administration, and check the heart rhythm, produce records, pass drugs to physicians and nurses, and serve as CPR staff. CPR involves a large number of processes, and requires rapid responses. The participation of pharmacists in time management and drug administration, playing specific roles, has promoted role-sharing among physicians, nurses, and pharmacists, as well as the establishment of a "resuscitation team" in the hospital. Emergency medicine is in a difficult situation. We believe that our efforts have helped pharmacists contribute to emergency care and provide high-quality CPR.