Overview of Ocular Side Effects of Selinexor.

BACKGROUND: The aim of this review is to elucidate the type and frequency of ocular adverse events associated with selinexor with a goal to quantify the occurrence of these events in our investigator-initiated trial. METHODS: We retrospectively reviewed medical records of 174 patients treated with at least one dose of selinexor in combination with multiple standard chemotherapy or immunotherapy agents between July 2015 and July 2020 at a comprehensive cancer center in the U.S. All reported ocular adverse events were assessed. RESULTS: A total of 174 patient medical records were reviewed. All patients received at least one dose of selinexor in combination with multiple standard chemotherapy or immunotherapy agents in our cohort of patients with advanced malignancies. A total of 34 (19.54%) patients experienced 37 ocular adverse events. The most frequently reported ocular symptom was blurred vision, which was reported in 22 (12.64%) patients. The most frequently reported treatment-related adverse event was dry eye syndrome reported in 21 (12.1%) patients, and 19 (10.9%) of them were diagnosed with mild dry eye. The second most common treatment-related adverse event was the progression of age-related nuclear sclerosis (cataract) reported in 7 (4.0%) patients. None of the ocular adverse events required therapy discontinuation. CONCLUSION: Our findings highlight that ocular adverse events associated with oral selinexor were mild. The most frequently reported ocular treatment-related adverse events were mild dry eye and progression of age-related nuclear sclerosis. None of the ocular adverse events required therapy discontinuation. IMPLICATIONS FOR PRACTICE: Patients receiving selinexor in combination with multiple standard chemotherapy or immunotherapy agents were reviewed, with a total of 34 patients experiencing 37 ocular adverse events. Findings highlight that ocular adverse events associated with oral selinexor were mild. The most frequently reported ocular treatment-related adverse events were mild dry eye and progression of age-related nuclear sclerosis. None of the ocular adverse events required therapy discontinuation.

Dual antiangiogenic inhibition: a phase I dose escalation and expansion trial targeting VEGF-A and VEGFR in patients with advanced solid tumors.

PURPOSE: Angiogenesis plays a pivotal role in tumor growth and metastasis. Sorafenib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR), combined with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF-A), would vertically inhibit VEGF/VEGFR signaling. A phase I trial was performed to assess safety, maximum tolerated dose (MTD), and clinical correlates. EXPERIMENTAL DESIGN: Patients with advanced solid tumors refractory to standard therapy were eligible. In cohorts of escalating doses, patients received sorafenib daily for 28 days and bevacizumab every two weeks. Clinical correlates included VEGF polymorphisms. Expansion cohorts of responding tumor types were enrolled. RESULTS: One hundred fifteen patients were treated, and the MTD was identified as 200 mg twice daily sorafenib and 5 mg/kg bevacizumab every two weeks. Median number of prior therapies was four. Twenty-nine patients (25 %) achieved stable disease ≥6 months; six patients (5 %) achieved a partial response (total SD ≥ 6 months/PR=35 (30 %)). 76 patients (66 %) experienced adverse events of grade 2 or higher, most commonly hand and foot syndrome (n = 27, 24 %) and hypertension (n = 24, 21 %). Dose-limiting toxicity occurred in eight patients (7 %), and 45 patients (39 %) required dose reduction for toxicity. Grade 3 and 4 hypertension was associated with longer time to treatment failure, overall survival, and higher response rate. CONCLUSIONS: Combination sorafenib and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with advanced solid tumors.

Prevalence of complementary medicine use in a phase 1 clinical trials program: the MD Anderson Cancer Center Experience.

BACKGROUND: A key end point of early cancer clinical trials is the assessment of toxicities and their possible association with new experimental drugs. Therefore, the concurrent use of complementary and alternative medicine (CAM) in patients with advanced malignancies seen in a dedicated phase 1 clinic was evaluated. METHODS: An investigator-designed survey was anonymously completed by patients seen in the phase 1 clinic. Pharmacologic CAM included any oral, topical, or intravenous agent, including vitamins, dietary supplements, and herbal products. Nonpharmacologic CAM included prayer, meditation, hypnosis, massage, and acupuncture. RESULTS: Of the 404 patients approached about completing the CAM survey, 394 (98%) agreed to respond, and 309 (78%) surveys were returned. Of those 309 patients, 162 (52%) used 1 or more CAM. Of the 162 CAM users, 77% utilized pharmacologic CAM, 71% used nonpharmacologic CAM, and 48% used both modalities. The most frequent CAM used were vitamins (70%), prayer (57%), and herbal products (26%). CAM utilization was not significantly associated with race, age, level of education, employment, or income level but was used more by women than men (P < .01). There was no statistically significant association between the use of CAM and quality of life as perceived by patients. Of the CAM users, 43% of patients had been using CAM for >5 years. Only 5% reported having side effects from using CAM, whereas 23% did not fully disclose their CAM use to their physicians. CONCLUSIONS: CAM usage is common in patients with advanced malignancies seen in a phase 1 clinic.

Update on aurora kinase inhibitors in gynecologic malignancies.

Aurora kinases are essential for the regulation of chromosome segregation and cytokinesis during mitosis and play a role in tumorigenesis and tumor progression in humans. Aurora kinase A and Aurora kinase B are overexpressed in some gynecologic cancers, and their overexpression is associated with poor prognosis. Thus, targeting of Aurora kinases has become an attractive strategy for pharmaceutical companies, who have developed more than 30 Aurora kinase inhibitors for treatment of cancers. Some of these inhibitors have been shown to be effective in targeted therapies for human cancer, and others are currently being investigated. In this review, we summarize the most recent advances in preclinical studies and clinical trials of patented Aurora kinase inhibitors for gynecologic tumors.