Abstract 1820P
Background
Skin toxicity is one of the most common toxic effects of the taxanes. We aimed at assessing the effect on skin of paclitaxel in a group of gynecological cancer (GC) patients regardless of the presence of clinical cutaneous manifestations and in an in vitro 3D model of skin.
Methods
Between May-November 2019 patients with GC FIGO I-IV treated with paclitaxel (either weekly or 3-weekly) were included. A control group of healthy volunteers was also analyzed. Parameters of hydration, transepidermic water loose (TEWL), cutaneous fat (CF), pigmentation and erythema, desquamation and skin thickness were measured before starting chemotherapy, after 3 and after 6 cycles (6C). These parameters were assessed with different skin meters and cutaneous sonography. For the in vitro study a 3D model with human primary keratinocytes (PHK) and primary fibroblast BALB/3T3 was created. In addition, melanocytes and microvascular dermic cells were also analyzed. IL-1a, IL-6 e IL-8 were quantified by ELISA. The expression of genes and proteins related with elasticity, melanogenesis, hydration and apoptosis was assessed by qPCR and western blot.
Results
20 GC patients and 20 controls were included. No differences between basal GC and controls were seen. Only 4 patients (20%) had skin toxicity (grade 1). Paclitaxel reduced significantly (p<0.05) parameters related with hydration (-18.7%±5.4), TEWL (-26.7%±8.6), CF (-45.3%±8.2), elasticity (-47.2%±8.3)and thickness (-16.45%±1.58) and increased significantly desquamation (+14.9±3,2), pigmentation (+6.7%±1.9)and redness (13.9%±4.1)between basal and 6C determinations. In vitro analyses showed an increase in PHK apoptosis and an increase in melanogenesis related genes TYR, TYRP1 and DCT in melanocytes. Paclitaxel reduced formation of endothelial tube. In the 3D skin model molecular markers of elasticity (COL1, ELN, FN1), hydration n (AQP3), ROS regulation (NOX4, Nrf2, SOD1), angiogenesis (VEGF and eNOS), apoptosis and senescence (p53, Bcl2 and p21) and cytokines (IL-1, Il-6 and IL-8) were significantly altered.
Conclusions
Six courses of paclitaxel induce measurable non-symptomatic alterations in skin. Cutaneous effects are related to gene expression and to changes in cytokines production.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jose Alejandro Perez Fidalgo.
Funding
Department of Pharmacology. Universidad de Valencia.
Disclosure
J.A. Perez Fidalgo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Ability Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: GSK. A. Cervantes: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Serono; Roche; Bayer; Servier; Research grant/Funding (institution): Genentech; BMS; MSD; Beigene; Lilly; Novartis; Takeda; Astellas; Fibrogen; Speaker Bureau/Expert testimony: Pierre Fabre. All other authors have declared no conflicts of interest.