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Abstract

Objective

To develop a slow-release carboplatin formulation for intratumoral administration to cats.

Design

Preliminary study to analyze pharmacokinetic effects of purified sesame oil in the carboplatin formulation for intratumoral administration, and a second study to evaluate the efficacy and toxicosis of intratumoral administration of carboplatin in purified sesame oil.

Animals

23 cats with squamous cell carcinomas of the nasal plane.

Procedure

Eight cats with advanced-stage tumors were submitted to intratumoral administration of 100 mg of carboplatin/m2 of body surface area, with or without purified sesame oil, using a two-period, cross-over design. Fifteen additional cats were treated by intratumoral administration of carboplatin in purified sesame oil. Four weekly intratumoral chemotherapy injections of carboplatin in purified sesame oil at a dosage of 1.5 mg/cm3 of tissue were given.

Results

Purified sesame oil in the formulation significantly reduced systemic exposure to carboplatin and drug leakage from the sites of injection. Cumulative effects of repeated intratumoral administrations on plasma concentrations of carboplatin were not observed. Systemic toxicosis was not observed, and local toxicosis was minimal. Healing of ulcerated lesions was not compromised. Rates of complete clinical tumor clearance and complete response were 67 and 73.3%, respectively. Product-limit estimates of mean progression-free survival times was 16 ± 3.3 months. The 1-year progression-free survival rate was 55.1 ± 13%. Local recurrence was observed in 7 cats; 4 had marginal tumor recurrence, and 3 had in-field and marginal tumor recurrence.

Conclusions

Intratumoral carboplatin chemotherapy is safe and effective for cats with squamous cell carcinoma of the nasal plane. Future studies to improve treatment efficacy could include evaluation of increased dose-intensity as well as combination of this modality with radiotherapy.

Clinical Relevance

Intratumoral administration of carboplatin in a water-sesame-oil emulsion was found to be a practical and effective new treatment for facial squamous cell carcinomas in cats.

Free access
in American Journal of Veterinary Research

SUMMARY

Piroxicam and other nonsteroidal anti-inflammatory drugs (nsaid) have antitumor activity against naturally acquired cancer in dogs and human beings, and against experimentally induced tumors in rodents. We are investigating potential mechanisms of nsaid antitumor activity. The direct cytotoxicity of piroxicam, indomethacin, and aspirin against 4 canine tumor cell lines (transitional cell carcinoma, squamous cell carcinoma, melanoma, and soft tissue sarcoma) was determined in short-term growth rate assays and in clonogenic assays. Piroxicam was evaluated alone and in combination with the lipoxygenase inhibitor zileuton, and in combination with the chemotherapeutic agents cisplatin and carboplatin. The 50% inhibitory concentrations (lC50) against melanoma cells in short-term growth rate assays were: 530 μM piroxicam, 180 μM indomethacin, and greater than 1 mM aspirin. These IC50 values were over 10 times greater than serum concentrations of these drugs that could safely be achieved in vivo. The IC50 of zileuton combined with piroxicam (280 μM) was not different from the IC50 of zileuton alone (230 μM; anova P = 0.47) in melanoma cells. Similarly, addition of piroxicam did not alter the IC50 of either cisplatin (1.6 μM) or carboplatin (6.1 μM). These results suggest that nsaid, at serum concentrations achievable in vivo, do not have direct cytotoxicity against canine tumor cells tested. It is unlikely that the in vivo antitumor activity of nsaid is attributable to a direct cytotoxic effect.

Free access
in American Journal of Veterinary Research