Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities

Background Epidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention and treatment of these untoward events. The purpose of this panel was to develop evidence-based recommendations for EGFRI-associated dermatologic toxicities. Methods A multinational, interdisciplinary panel of experts in supportive care in cancer reviewed pertinent studies using established criteria in order to develop first-generation recommendations for EGFRI-associated dermatologic toxicities. Results Prophylactic and reactive recommendations for papulopustular (acneiform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis/fissures, and paronychia are presented, as well as general dermatologic recommendations when possible. Conclusion Prevention and management of EGFRI-related dermatologic toxicities is critical to maintain patients’ health-related quality of life and dose intensity of antineoplastic regimens. More rigorous investigation of these toxicities is warranted to improve preventive and treatment strategies

The petrosal artery and its variations: a comprehensive review and anatomical study with application to skull base surgery and neurointerventional procedures

Background: The petrosal artery supplies several structures at the skull base and is often the focus of various neurointerventional procedures. Therefore, knowledge of its anatomy and variations is important to surgeons and interventionalists. Materials and methods: Twenty latex injected cadaveric heads (40 sides) underwent microsurgical dissection of the petrosal artery. Documentation of the course of the artery and its branches were made. Measurements of the petrosal artery’s length and diameter were performed using microcalipers. Results: A petrosal artery was identified on all sides. The mean length and diameter of the artery within the middle cranial fossa was 2.4 cm and 0.38 mm, respectively. Branches included the following: dural, ganglionic, V3 branches, branches extending through the foramen ovale, branches directly to the greater petrosal and lesser petrosal nerves, branches to the floor of the hiatus of the greater and lesser petrosal nerves, branch to the arcuate eminence, and superior tympanic artery. No statistically significant differences were noted between male and female specimens, but right-sided petrosal arteries were in general, larger in diameter than left sides. Conclusions: A thorough anatomical knowledge of the petrosal artery and to its relationship to the facial nerve and other neurovascular structures is necessary to facilitate effective endovascular treatment and to preclude facial nerve complications

A phase II study to evaluate the safety and efficacy of OQL011 on VEGFR inhibitor-associated hand-foot-skin reaction in cancer patients.

TPS12132 Background: Hand-Foot Skin Reaction (HFSR) is frequently associated with the use of multi-targeted tyrosine kinase inhibitors of the vascular endothelial growth factor receptor (VEGFRi) such as cabozantinib, regorafenib, sunitinib, and lenvatinib. HFSR affects the skin on the palms and soles and is manifested as edema, erythema, hyperkeratosis, and bullae, leading to a decrease in quality of life and interruptions in dosing. The incidence of HFSR differs among VEGFRi, ranging from 5-60% (all grades) and 1-18% (grade 3). To date, there is no FDA approved treatment for HFSR, and marginal benefit has been shown with topical urea or steroids. Although not fully elucidated, the pathogenesis of HFSR has been associated with impaired vascular repair mechanisms, caused by inhibition of VEGF signaling pathways. We hypothesize that topical stimulation of VEGFR through OQL011 will decrease the severity of HFSR symptoms via local upregulation of the VEGF/VEGFR related signaling pathways. Methods: NCT04088318 is a phase 2, double-blind, randomized controlled trial to evaluate the safety and efficacy of OQL011 compared to vehicle control in the treatment of moderate to severe HFSR in patients on VEGFRi therapy. Eligible patients will have ≥ grade 2 palmar plantar erythrodysesthesia (PPE). The study is expected to enroll 112 patients in two parts. In the first part, 42 patients will apply 0.2% OQL011 topical ointment or vehicle control (2:1 randomization) TID for six weeks. In Part 2, 70 subjects will be randomized into two additional dose levels or vehicle control in a 2:2:1 ratio. The two dose levels selected will be based on the efficacy and safety results of Part 1. The primary efficacy endpoint is improvement of NCI CTCAE v5.0 PPE to grade ≤1 by week 3. Photographs of the affected areas will be taken at Day 0, 7, 14, 21 and 42 timepoints. Superiority test will be performed to compare treatment groups, and the exposure-response relationship will be explored. In addition, an investigator global assessment (IGA) for HFSR will be used in this trial to specifically assess skin recovery and is proposed to be a new evaluation tool. The validity of IGA criteria will be evaluated by assessing the inter-rater and intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient reported outcomes including Visual Analog Scale of Pain, Hand-foot Quality of Life questionnaire will also be evaluated. This study began enrolling patients in December 2019 and is ongoing. Clinical trial information: NCT04088318. </jats:p