Pilot study evaluating the tolerability of a 3 Gy x 10 daily fraction 3D-conformal palliative radiation therapy protocol plus toceranib for the treatment of measurable carcinomas in the dog

The use of radiation therapy in conjunction with small molecule inhibitors is an appealing treatment combination for non-resectable carcinomas, which tend to be locally invasive with variable risk of locoregional metastasis. This prospective, pilot study aimed to evaluate the tolerability and adverse event profile of concurrent toceranib and palliative-intent radiation therapy (PRT) in dogs with measurable carcinoma and to secondarily evaluate short-term measurable tumor response. Fifteen dogs with measurable carcinoma received toceranib and 3D-conformal PRT in 3 Gy/fraction for 10 daily fractions. Adverse events were graded using standard schemes and tolerability was followed via quality-of-life questionnaires during the 12-week treatment period. Thirteen dogs (87%) experienced acute radiation toxicity, graded as severe in three dogs. All dogs experienced toceranib toxicity, graded as severe in one dog. Seven dogs (47%) completed the 12-week study protocol; four were withdrawn due to toxicity and/or associated poor quality of life and four developed progressive disease. Based on these preliminary results, this 3D-conformal chemoradiation protocol should be considered with caution and only with proper owner education on potential toxicity. More conformal treatment planning techniques or alternative protocols should be investigated for improved tolerability.