Abstract
BackgroundEffective therapies for transitional cell carcinoma (TCC) are limited, with objective response rates to most chemotherapeutic regimens below 20%. The purpose of this study was to investigate the biologic activity of combined toceranib phosphate and vinblastine chemotherapy for treatment of TCC. A secondary objective was to compare the utility of Computed Tomography (CT) and abdominal ultrasound (AUS) in tumor response assessments.ResultsDogs with TCC received vinblastine at 1.6 mg/m2 every 2 weeks and toceranib at 2.5–2.75 mg/kg on Monday/Wednesday/Friday. Tumor monitoring was achieved through CT and AUS. Five patients completed the 16-week study. Based on AUS assessments, 3 dogs experienced biologic response to therapy including partial responses (PR, n = 2) and stable disease (SD, n = 1). Based on CT, 5 dogs experienced a biologic response (n = 2 PR, n = 3 SD). Both imaging modalities (ultrasound and CT) were found to provide repeatable measurements between operators, however agreement between operator measurements was greater when CT images were used to assess tumor size.ConclusionsThe combination of toceranib and vinblastine did not result in improved response rates. While agreement in tumor volume assessments between both AUS and CT were excellent between operators, this did not extend to assessment of tumor response. The higher rate of concordance between operators when assessing response to treatment with CT suggests that CT should be considered for future clinical trials involving canine bladder TCC to improve the accuracy and repeatability of tumor measurement. The data suggest that response to therapy as assessed by AUS or CT do not predict duration of clinical response.
Highlights
Effective therapies for transitional cell carcinoma (TCC) are limited, with objective response rates to most chemotherapeutic regimens below 20%
Vinblastine has been used as a single agent to treat canine TCC resulting in a 36% partial response rate, these were relatively short lived as the progression free survival was only 4 months, with an overall survival time of approximately 5 months [22]
Two patients had enlarged regional lymph nodes with the potential for metastasis, though disease spread was not confirmed by FNA due to the risk of seeding the peritoneum
Summary
Effective therapies for transitional cell carcinoma (TCC) are limited, with objective response rates to most chemotherapeutic regimens below 20%. Several different chemotherapy agents have been used to treat canine TCC including carboplatin, cisplatin, doxorubicin, cyclophosphamide and intravesicle thiotepa. None of these drugs result in objective response rates greater than 10– 15% [3, 4]. Piroxicam has been combined with the chemotherapeutic mitoxantrone resulting in an objective response rate of approximately 35% [20] This drug combination is often used to treat TCC the reported median survival time is only 291 days from the date of diagnosis. Vinblastine has been used as a single agent to treat canine TCC resulting in a 36% partial response rate, these were relatively short lived as the progression free survival was only 4 months, with an overall survival time of approximately 5 months [22]. The use of metronomic chlorambucil has showed some clinical efficacy with a reported biological response rate of 68%, most of these consisted of stable disease [23]
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