Tissue distribution of epirubicin after severe extravasation in humans

• Published in: Cancer chemotherapy and pharmacology Vol. 88; no. 2; pp. 203 - 209
• Main Authors: Nedomansky, Jakob, Haslik, Werner, Pluschnig, Ursula, Kornauth, Christoph, Deutschmann, Christine, Hacker, Stefan, Steger, Günther G., Bartsch, Rupert, Mader, Robert M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2021; Springer Nature B.V
• Subjects: Aged; Anthracycline; Anthracyclines - adverse effects; Anthracyclines - pharmacokinetics; Anthracyclines - therapeutic use; Antibiotics, Antineoplastic - adverse effects; Antibiotics, Antineoplastic - pharmacokinetics; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Cancer Research; Cancer therapies; Chemotherapy; Chromatography; Cytokines; Cytokines - metabolism; Cytotoxicity; Doxorubicin; Doxorubicin - adverse effects; Doxorubicin - pharmacokinetics; Doxorubicin - therapeutic use; Drug dosages; Epirubicin; Epirubicin - adverse effects; Epirubicin - pharmacokinetics; Epirubicin - therapeutic use; Erythema; Extravasation; Female; Growth factors; High-performance liquid chromatography; Hospitals; Humans; Inflammation; Inflammation - metabolism; Lesions; Male; Medicine; Medicine & Public Health; Middle Aged; Necrosis; Necrosis - chemically induced; Necrosis - metabolism; Oncology; Original; Original Article; Patients; Pharmacology; Pharmacology/Toxicology; Plastic surgery; Skin & tissue grafts; Skin Diseases - drug therapy; Skin Diseases - metabolism; Surgery; Surgical Flaps - pathology; Tissue Distribution - physiology; Wound healing; Wound Healing - drug effects; Anthracycline; Tissue concentration; Extravasation; Surgery; HPLC
• ISSN: 0344-5704; 1432-0843; 1432-0843
• DOI: 10.1007/s00280-021-04280-8

Purpose As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose–toxicity relation. Methods From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin: 5 subjects; doxorubicin: 1 subject). Results After extravasation, tissue concentrations were highly variable with an individual anthracycline distribution pattern ranging from a few nanograms up to 17 µg per 100 mg tissue, which indicated a substantial difference in tissue sensitivity among patients. The resection borders coincided with the extension of the erythema and guided the surgical intervention after demarcation of the lesion, which occurred usually 2 or 3 weeks after extravasation. At that time, drug was hardly detected at the resection borders. Wound drains were negative for the extravasated drugs while showing a time profile of vascular growth factors and inflammatory cytokines, which was highly similar to routine surgery. In all six patients, surgical debridement with immediate wound closure led to healing within approximately 2 weeks, when therapy was resumed in all patients with reasonable time delay. Conclusion Surgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority.