A pilot study of toceranib/vinblastine therapy for canine transitional cell carcinoma

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.

Outcome and prognostic factors in medically treated canine prostatic carcinomas: A multi‐institutional study

“…Similarly, response to treatment was typically based on imaging findings. However, in a recent study of dogs with bladder TCC receiving treatment, follow‐up imaging was performed using both CT and AUS; as seen with some dogs in this study, imaging of PC can have discordant results when compared to clinical signs. It is of the author's opinion that ultrasound or CT lesions are a poor measure of disease progression or response, and improvements are needed in this area.…”

“…However, in a recent study 32 canine Gleason score has recently been proposed. 36 Similarly in human medicine, histopathology is able to identify high-grade prostate intra-epithelial neoplasm (HG-PIN) and atypical small acinar proliferation as premalignant histopathologic lesions that raise concern for development of prostate cancer.…”

Tumour angiogenesis, anti‐angiogenic therapy and chemotherapeutic resistance

“…Toceranib and masitinib have been approved for veterinary use in dogs, particularly for mast cell tumours . However, a range of anti‐angiogenic drugs, either alone or in combination, has been used to treat a wide variety of canine and feline neoplasms, including osteosarcomas, melanomas, fibrosarcomas, histiocytic sarcomas, haemangiosarcomas, lymphomas and prostatic, thyroid, nasal, gastric, mammary, pulmonary, biliary, salivary, anal sac and urinary bladder carcinomas …”

“…In the majority of these veterinary studies, tocerinab was used, sometimes alone [29][30][31][32][33][34][35][36][37] or, more commonly, in combination with other drugs such as cyclophosphamide (belonging to the nitrogen mustard group of alkylating agents), 38,39 vinblastine (an antimitotic alkaloid), 40,41 carboplatin (a platinum-containing complex), 42,43 lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosurea (or CCNU), which belongs to the nitrosurea group of alkylating agents), [44][45][46] doxorubicin (an anthracycline antibiotic) [47][48][49] and piroxicam (a nonsteroidal anti-inflammatory drug (NSAID) with cyclooxygenase (COX)-2 inhibiting properties). 38,[50][51][52] Masitinib has also been evaluated in dogs.…”

Canine urinary bladder transitional cell carcinoma tumor volume is dependent on imaging modality and measurement technique

“…Mapping of the bladder to characterize the location of the transitional cell carcinoma tumor is poignant in the clinical evaluation and staging for disease to determine if surgery is an option . Even when surgical excision is possible, the goal of surgery may be limited to diagnostic purposes or for palliation of clinical signs due to the inability to obtain appropriate surgical margins and the effect of field carcinogenesis on the remaining urinary bladder tissue …”