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Objectives During crizotinib clinical evaluation, visual disturbances, generally of grade 1 severity, were frequently reported adverse events (AE). Consequently, ophthalmologic assessments were included in a patient subgroup enrolled in PROFILE 1001 (NCT00585195), a phase 1, open-label, single-arm trial of crizotinib in patients with advanced non-small-cell lung cancer and are reported here. Materials and methods At least 30 patients were required to undergo ophthalmologic assessments, including: best-corrected visual acuity (BCVA), refractive error, pupil size, slit-lamp anterior segment biomicroscopy, intraocular inflammation, intraocular pressure, retinal fundoscopic exams, fundus photography, ocular characteristics, and optical coherence tomography (OCT). Scheduled assessments included those at baseline, Cycle 1 Day 15, Cycle 3 Day 1 (C3D1), annually during treatment, and end of treatment (28 days after last crizotinib dose). Results Thirty-three patients completed all required ophthalmologic assessments through C3D1, and 22 (66.7 %) had abnormal findings on ≥1 ophthalmologic test. Clinically important changes were ≥2-line loss in BCVA in 10 patients (30.3 %), >±1.25-diopter change in refractive error in 3 patients (9.1 %), >±2-mm change pupillary diameter change in 3 patients (9.1 %), and >50 μm increase in OCT center point thickness in 7 patients (21.2 %). Three patients (15 %) reported clinically significant abnormalities in anterior segment biomicroscopy (grade 1 cataract [n = 2], grade 1 Visual Impairment [n = 1]). No permanent treatment discontinuations were associated with ophthalmologic findings changes. Twenty-four patients (72.7 %) reported ≥1 ocular all-causality treatment-emergent AE (TEAE); none required dose reduction or permanent discontinuation, but 2 required temporary dosing interruption. Although TEAEs and ophthalmologic findings may not have occurred concurrently, of 24 patients with ≥1 all-causality ocular TEAE, 18/24 (75.0 %) had ≥1 abnormal ophthalmologic finding and 6/24 (25 %) had none; and of 9 patients without an all-causality ocular TEAE, 4/9 (44.4 %) had ≥1 abnormal ophthalmologic finding and 5/9 (55.6 %) had none. Of the 18 patients with ≥1 abnormal ophthalmologic finding, 9 (50 %) had preexisting ocular conditions. Conclusion During crizotinib treatment, ophthalmologic changes from baseline did not appear to be associated with patient-reported ocular TEAEs. Abnormal ophthalmologic findings occurred in the context of preexisting conditions for a number of patients. No ophthalmologic changes from baseline or ocular all-causality TEAEs required permanent treatment discontinuation.

Introduction We retrospectively analyzed the effects of crizotinib on serum creatinine and creatinine-based estimated glomerular filtration rate (eGFR) in patients with anaplastic lymphoma kinase–positive advanced NSCLC across four trials (NCT00585195, NCT00932451, NCT00932893, and NCT01154140). Methods Changes from baseline data in serum creatinine and eGFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation, were assessed over time. eGFR was graded using standard chronic kidney disease criteria. Results Median serum creatinine increased from 0.79 mg/dL at baseline to 0.93 mg/dL after 2 weeks of treatment (median percentage increase from baseline, 21.2%), was stable from week 12 (0.96 mg/dL) to week 104 (1.00 mg/dL), and decreased to 0.90 mg/dL at 28 days after last dose (median percentage increase from baseline, 13.1%). Median eGFR decreased over time (96.42, 80.23, 78.06 and 75.45 mL/min/1.73 m2 at baseline, week 2, week 12, and week 104, respectively) and increased to 83.02 mL/min/1.73 m2 at 28 days after the last dose. Median percentage decrease from baseline was 14.9%, 17.0%, and 10.4% at week 2, week 12, and 28 days after last dose of crizotinib, respectively. Overall, 12.6% of patients had a shift from eGFR grade less than or equal to 3a (≥45 mL/min/1.73 m2) at baseline to greater than or equal to 3b ( Conclusions Crizotinib resulted in a decline in creatinine-based estimates of renal function mostly over the first 2 weeks of treatment. However, there was minimal evidence of cumulative effects with prolonged treatment and these changes were largely reversible following treatment discontinuation, consistent with previous reports suggesting this may be predominantly an effect on creatinine secretion as opposed to true nephrotoxicity.

Purpose To assess doctor–patient communication in patients with glaucoma. Design Observational cohort study. Participants Twenty-three ophthalmologists and 50 patients with glaucoma. Methods Doctor–patient encounters were audio- and videotaped and analyzed using validated sociolinguistic approaches. After the visit, the doctor and the patient completed questionnaires, and patients were interviewed using a semistructured, patient-centered protocol. Main Outcome Measures Summary statistics about doctor–patient encounters, assessment of alignment of attitudes between patients and doctors, and patient admission to missing doses. Results Physicians spent an average of 8.0 (standard deviation [SD], 3.1; median, 7.8) minutes in the room with the patient and an average of 5.8 (SD, 2.4; median, 7.5) minutes talking with the patient, delivering 70% of all spoken words and asking two thirds of all questions. Glaucoma-related discussion occupied 50% of talk time and was focused primarily on examinations and treatment (25%). One third of discussions addressed ocular issues other than glaucoma. Virtually all physician questions (94%) were closed ended. Most patient questions were about intraocular pressure (20% of visits), details of the medication regimen (20%), disease status (14%), and testing (12%). Although physicians and patients were aligned in believing that the physician should control the visit agenda, physicians tended to support greater physician control of decision making than did patients. Physicians failed to identify most patients who admitted to missing doses, a surrogate for nonadherence, stating that 10 of 13 in this category were taking drops "all" or "most" of the time. Physician interviews detected 3 of the 11 patients whose postvisit questionnaire indicated missing a dose in the last week compared with 11 of the 11 detected by the postvisit research interview. Patients who stated they had missed doses recently reported being less satisfied with the doctor–patient encounter than those who did not. Conclusions Doctor–patient dialogue was universally physician centered; physicians spoke 70% of the words and asked closed-ended questions that restricted the patient's contribution to "yes/no" or brief responses. A minority of physicians ever asked patients if they had questions. In contrast with the patient-centered research interview, doctors' physician-centered communication failed to identify most patients who had missed doses. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Objective To use multiple data sources to determine drivers of patient adherence to topical ocular hypotensive therapy. Design Retrospective database and chart reviews in combination with prospective patient surveys. Diverse medical environments where insured patients in the research database seek care. Participants Three hundred patients with a new claim diagnosis for open-angle glaucoma who initially were prescribed one of three prostaglandins and 103 physicians participating in the same medical plans. Methods A structured interview addressing self-reported adherence, experiences with medication, communication with the physician, and health-related beliefs associated with adherence behavior was administered to surveyed patients. Phone interviews were conducted with participating ophthalmologists. Main Outcome Measure Of adherence, medication possession ratio. Results Eight variables were associated independently with a lower medication possession ratio: (1) hearing all of what you know about glaucoma from your doctor (compared with some or nothing); (2) not believing that reduced vision is a risk of not taking medication as recommended; (3) having a problem paying for medications; (4) difficulty while traveling or away from home; (5) not acknowledging stinging and burning; (6) being nonwhite; (7) receiving samples; and (8) not receiving a phone call visit reminder. The multivariate model explained 21% of the variance. Conclusions These findings indicate that doctor–patient communications and health-related beliefs of patients contribute to patient adherence. Patient learning styles that are associated with less concern about the future effects of glaucoma and the risks of not taking medications are associated with lower adherence. Specifically, knowledge about potential vision loss from glaucoma is a critical element that tends to be missed by more passive doctor-dependent patients who tend to be poorly adherent. These findings suggest that educational efforts in the office may improve patient adherence to medical therapies.