Can Epirubicin Be Used in Laryngology Practice Like Mitomycin? An Experimental and Pioneering Study

Original Article Iranian Journal of Otorhinolaryngology, Vol.37(5), Serial No.142, Sep-2025 Can Epirubicin Be Used in Laryngology Practice Like Mitomycin? An Experimental and Pioneering Study Erdem Koroglu1, Selahattin Genc1, Serdar Baser1, Ferit Bayakır 1, Ahmet Tugrul Eruyar 2, Busra Yaprak Bayrak2 * Abstract Introduction: Epirubicin and mitomycin-C share similar mechanisms of action, with both exhibiting antiproliferative effects by inhibiting DNA and protein synthesis. While the efficacy of mitomycin-C in laryngology is well established, this study aims to investigate whether epirubicin can produce comparable clinical outcomes in this field. Materials and Methods: Ten rabbits were included in this experimental study. A thermal injury was created at the posterior commissure using a conchal probe. Following the injury, one group was treated with mitomycin-C, while the other received epirubicin. After a six-week post-treatment period, the rabbits were euthanized, and both macroscopic and microscopic evaluations were performed to assess stenosis, scarring, granulation tissue, necrosis, and ulceration. Two pathologists, blinded to the treatment groups, independently examined the histological samples. Results: Macroscopically, no significant differences were observed between the two groups in terms of scarring, synechiae, or granulation tissue formation at the posterior commissure. However, the mitomycin-C group demonstrated a relatively milder tissue response. Microscopic analysis revealed grade 3 collagen deposition in one rabbit and grade 1 in two rabbits from the epirubicin group. In comparison, the mitomycin-C group showed grade 1 deposition in two rabbits and grade 2 in another two. The average fibroblast count was 83.3 in the epirubicin group versus 59 in the mitomycin-C group. Conclusions: Although this pioneering study does not provide conclusive evidence that epirubicin is as effective as or superior to mitomycin-C in laryngology, it highlights epirubicin’s potential as a promising candidate for further investigation in the treatment of laryngeal conditions. Keywords: Epirubicin; Mitomycin-C; Laryngeal Posterior Commissure; Laryngostenosis Received date: 22 Apr 2025 Accepted date: 31 May 2025 *Please cite this article; Koroglu E, Genc S, Baser S, Bayakır F, Eruyar AT, Bayrak BY. Can Epirubicin be used in Laryngology Practice like Mitomycin? An Experimental and Pioneering study. Iran J Otorhinolaryngol. 2025:37(5):247-252. Doi: 10.22038/ijorl.2025.87024.3938 1University of Health Sciences Kocaeli Derince Health Research and Application Center, Otorhinolaryngology and Head & Neck Surgery Clinic. 2 Kocaeli University Faculty of Medicine, Pathology Clinic. *Corresponding author: University of Health Sciences Kocaeli Derince Health Research and Application Center, Otorhinolaryngology and Head & Neck Surgery Clinic. Kocaeli-Turkey. E-mail: Copyright©2025 Mashhad University of Medical Sciences. This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 International License https://creativecommons.org/licenses/by-nc/4.0/deed.en 247 Koroglu E, et al Introduction Laryngology, a subspecialty within otolaryngology, often requires innovative therapeutic strategies to manage conditions such as laryngeal stenosis and scarring. Laryngostenosis refers to the narrowing of the airway within the larynx, resulting from various etiologies, including post-surgical fibrosis, trauma, or chronic inflammation (1,2). Current treatment modalities, such as surgical intervention and the use of mitomycin-C, offer variable success rates and often necessitate repeated procedures with prolonged recovery periods. The demand for novel therapeutic agents that can effectively regulate scar formation and enhance mucosal healing is increasingly emphasized in laryngology. Mitomycin-C has been established as an effective agent in reducing fibrosis and promoting mucosal repair following laryngeal surgery (3,4). It is currently used in a wide range of procedures involving stenosis correction in the lacrimal sac, larynx, trachea, choanal atresia, and esophageal strictures (5–8). Nonetheless, the search for alternative agents that offer comparable or superior outcomes continues. Epirubicin is a well-established chemotherapeutic agent, particularly in the treatment of breast cancer, due to its potent ability to inhibit cell proliferation and induce apoptosis in rapidly dividing cells (9). Its antiproliferative effects arise from its interference with DNA and RNA synthesis, similar to those of mitomycin-C. Given this shared mechanism of action, it is hypothesized that epirubicin may also prove effective in managing laryngeal conditions characterized by excessive fibroproliferation and scarring. This study evaluates the potential of epirubicin in laryngology and compares its effects with those of mitomycin-C. Materials and Methods This study was conducted by researchers certified in animal experimentation, with approval obtained from the local ethics committee (koü hadyek 4/3-2017). The authors affirm that all procedures adhered to national and institutional ethical guidelines concerning the care and use of laboratory animals. Generation of posterior glottic damage and its treatment with the active ingredient Ten 12-week-old white New Zealand rabbits, weighing between 2.1 and 2.4 kg, were included in the study. General anesthesia was achieved via intramuscular administration of xylazine (5 mg/kg) and ketamine (35 mg/kg). A metal tongue depressor was bent into an L-shape to retract the tongue, enabling visualization of the posterior glottis with a 0°, 4 mm rigid endoscope (Karl Storz GmbH & Co., Tuttlingen, Germany). A conchal probe from a coblator device (Coblator II, ArthroCare Corporation, USA) was used to induce thermal injury involving the posterior commissure, medial facets of the bilateral arytenoid cartilages, and the posterior third of the membranous vocal folds (Figure 1). Fig 1: Thermal injury was inflicted on the posterior commissure, including the medial facets of the arytenoid cartilages and the posterior 1/3 of the membraneous vocal cord. Direct laryngoscopic view. Asteriks; posterior commissure. Following the injury, the animals were randomly divided into two groups (n=5 per group). The first group received mitomycin-C (Mit-C), and the second group was treated with epirubicin (Ep). Mit-C powder was dissolved in injection-grade sterile water to a concentration of 0.4 mg/ml, based on literature-defined safe and effective doses. Epirubicin was diluted from a 50 mg/25 ml vial to a concentration of 0.5 mg/ml using sterile water, as no prior laryngological studies had established an appropriate concentration; this dose was therefore empirically estimated. The respective drug solutions were applied to cotton pads and placed on the injured posterior glottis for five minutes. To mitigate potential adverse effects such as necrosis, the treated area was subsequently rinsed (...truncated)