Injectable Chemotherapy Downstaged Oral Squamous Cell Carcinoma from Nonresectable to Resectable in a Rescue Dog: Diagnosis, Treatment, and Outcome

Abstract

This case report documents the diagnosis, treatment, and outcome of a nonresectable oral squamous cell carcinoma in a dog with initial poor prognosis. An approximately 4-year-old female Staffordshire Bull Terrier presented with a large mass on the front of lower jaw which was diagnosed as oral papillary squamous cell carcinoma by histopathology. CT scans revealed invasion of the cancer to the frenulum of the tongue. The mass was inoperable due to location, expansiveness, and metastatic lymph nodes. The dog received 4 treatments of intralesional hyaluronan-platinum conjugates (HylaPlat™, HylaPharm LLC, Lawrence, Kansas) at 3-week intervals. Clinical chemistry and complete blood count were performed one week after each treatment and results were within normal limits. Complications included bleeding due to tumor tissue sloughing, as well as a single seizure due to unknown causes. Upon completion of chemotherapy, CT showed that the mass had regressed and was no longer invading the lingual frenulum, and multiple lymph nodes were free of metastasis. The mass thus became resectable and the dog successfully underwent rostral bilateral mandibulectomy. Over one year after chemotherapy and surgery, the cancer remains in complete remission.

Intratumoral Cancer Chemotherapy with a Carrier-Based Immunogenic Cell-Death Eliciting Platinum (IV) Agent

“…Based on our experience with carrier-based Pt­(II) drugs, we hypothesized that localized delivery to tumor would further improve the activity of Pt­(IV). In addition, we believed a HA-based carrier could increase retention and tumor-associated lymph node uptake, while lessening RBC inactivation, a drawback of previous unsuccessful Pt­(IV) molecules including the clinically investigated drug sartaplatin. , The uniqueness of the HA-Pt­(IV) formulation in this work is manifested by the combination of at least three factors including - a lipophilic platinum­(IV) and its immunological properties as discussed below, a safe and pharmacokinetically tailored HA-based drug carrier demonstrated by previous animal studies, − ,,,− and a clinically feasible mode of intralesional delivery for spontaneous cancers based on the results of canine clinical trials. ,, The HA-Pt­(IV) formulation uses FDA-designated generally recognized as safe substances such as α-tocopherol, and biodegradable and biocompatible natural polysaccharide such as hyaluronic acid, which has been approved by the FDA for use as a dermal filler and as an intra-articular injection. These characteristics render HA-Pt­(IV) a clinically relevant molecule and justify the synthetic and testing efforts, which are discussed below in detail.…”

“…43,44 The uniqueness of the HA-Pt(IV) formulation in this work is manifested by the combination of at least three factors including -a lipophilic platinum(IV) and its immunological properties as discussed below, a safe and pharmacokinetically tailored HA-based drug carrier demonstrated by previous animal studies, 7−9,11,13,45−47 and a clinically feasible mode of intralesional delivery for spontaneous cancers based on the results of canine clinical trials. 10,14,15 The HA-Pt(IV) formulation uses FDA-designated generally recognized as safe substances such as α-tocopherol, and biodegradable and biocompatible natural polysaccharide such as hyaluronic acid, which has been approved by the FDA for use as a dermal filler and as an intra-articular injection. These characteristics render HA-Pt(IV) a clinically relevant molecule and justify the synthetic and testing efforts, which are discussed below in detail.…”

“…The intralesional HylaPlat demonstrated sustained release and prolonged retention of platinum in the lesion and the surrounding lymphatic basin in mice and rats, − and a remarkably high ratio of platinum in the tumor tissues compared to the systemic circulation in dogs . The improved targeted distribution of HylaPlat translated into anticancer efficacy against HNCs in laboratory mice − and in pet dogs with naturally occurring malignancies. , HylaPlat did not induce histologically evident injection-site reactions and systemic side effects such as renal and hepatic toxicities in rodents. Canine clinical studies, however, revealed myelosuppression, neutropenia, and liver injury, possibly because of the reactivity of the liberated platinum­(II) from the loosely bound hyaluronan (HA) carriers in the form of diaquated cisplatin that subsequently entered the circulatory system, bone marrow, and liver .…”

Application of Biocompatible Drug Delivery Nanosystems for the Treatment of Naturally Occurring Cancer in Dogs

“…The results confirmed that 23% of the animals had a complete regression of the disease, while 15% had a partial response [ 92 ]. Recently, Cai et al developed a cisplatin-hyaluronan nanoconjugate (HylaPlat) with the aim of treating a dog with a non-resectable oral squamous cell carcinoma with metastases in the local lymph nodes [ 97 ]. The dog was treated with 5–10 mg/m 2 of HylaPlat intra-lesionally injected every three weeks, for a total of four times.…”

“…In addition, the drug delivery system promoted the localization of cisplatin within the metastatic lymph nodes [ 98 ]. The dog reached a complete remission and maintained a stable condition for at least one year after the treatment ( Figure 3 ) [ 97 ].…”