Minimally invasive ethyl cellulose ethanol ablation in domesticated cats with naturally occurring head and neck cancers: Six cats

Abstract

It is difficult to retain tumoricidal doses of ethanol in large or unencapsulated tumours without causing intoxication or damaging surrounding tissue. Ethyl cellulose‐ethanol ablation (ECEA) overcomes this limitation by trapping ethanol intratumorally. To evaluate the safety of ECEA and to develop a clinically feasible workflow, a single‐arm pilot study was performed in cats with lingual/sublingual squamous cell carcinoma (SCC). Six cats underwent intratumoral injection of 6% ethyl cellulose in ethanol. Subjects were observed overnight. There was mild bleeding and transient hyperthermia, and injection site pain and swelling that improved with anti‐inflammatory drugs. Serum ethanol was minimally elevated; the mean concentration peaked 1 hour after injection (129 +/− 15.1 nM). Cats were rechecked at weeks 1 and 2; booster treatments were given in cats (n = 3) with stable quality of life and partial response to therapy. Recheck examinations were then performed monthly. The longest tumour dimension increased in each animal (progressive disease via cRECIST); however, estimated tumour volume was reduced in 3 of 6 cats, within 1 week of ECEA. All cats were euthanized (median survival time 70 days) because of local tumour progression and/or lingual dysfunction that was likely hastened by ECEA. ECEA is not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated. Further optimization may make ECEA a useful option for SCC at other oral sites in the cat, and for head and neck malignancies in other species.

Determining the Relationship between Delivery Parameters and Ablation Distribution for Novel Gel Ethanol Percutaneous Therapy in Ex Vivo Swine Liver

“…Injected ECE also exhibited decreased localized adverse events and increased overall survival in a syngeneic model of breast cancer, demonstrating the increased safety and efficacy of ECE in small animal models compared to ethanol alone [41]. Finally, injected ECE reduced tumor volume and was demonstrated as a feasible treatment for feline squamous cell carcinoma [42]. Overall, injected ECE ablation has the potential to address the need for a low-cost ablative therapeutic for the treatment of cancer in LMICs.…”

Systemic and Local Strategies for Primary Prevention of Breast Cancer

“…Controlling the diffusion of EtOH outside the ductal tree will be required to further minimize collateral tissue damage [101]. The use of ethyl cellulose as a gelling agent to limit ethanol diffusion has been reported for clinical treatment of venous malformation and in preclinical models of BC, cervical cancer, and liver cancer [152,[159][160][161][162][163][164][165]178]. We have shown that ethyl cellulose is compatible with a 70% EtOH ablative solution and with imaging contrast agents such as tantalum oxide nanoparticles in both mouse and rat models [152,153].…”

Biodegradable Polymers in Veterinary Medicine—A Review

“…Although tumor volume was reduced in some cats, concurrent lingual dysfunction occurred, excluding this kind of treatment from veterinary practice. However, further optimization of the applied treatment may make it an interesting minimally invasive option for curing oral, neck, and head cancers in cats and other animals [ 135 ]; Transdermal drug delivery—This involves drug delivery through the skin, and in veterinary medicine, it is a useful alternative to more traditional oral drug administration since it is non-invasive; avoids the gastric route, reducing potential gastric irritation and drug degradation; and has a reduced first-pass metabolism in the liver [ 134 , 136 ]. Cellulose and its derivatives can serve as a base for hydrogels with dispersed active ingredients, which perform better than creams and ointments due to their better adhesion, cooling effect, ease of removal, excellent drug-loading efficiency, and improved drug release.…”

“…Transdermal drug delivery—This involves drug delivery through the skin, and in veterinary medicine, it is a useful alternative to more traditional oral drug administration since it is non-invasive; avoids the gastric route, reducing potential gastric irritation and drug degradation; and has a reduced first-pass metabolism in the liver [ 134 , 136 ]. Cellulose and its derivatives can serve as a base for hydrogels with dispersed active ingredients, which perform better than creams and ointments due to their better adhesion, cooling effect, ease of removal, excellent drug-loading efficiency, and improved drug release.…”