Page 672 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

650 PART IV Specific Malignancies in the Small Animal Patient

TABLE 30.2 Study Results Reported for the Medical Therapy of Invasive Urothelial Carcinoma (iUC) in Dogs—cont’d
Number of Dogs: N 1 or N 2 /M 1 /Any Median Survival
VetBooks.ir Drug(s) Total/Evaluable for Metastasis, (% of CR (%) PR (%) SD (%) PD (%) PFI (d) From Start of Refs.
Tumor Response
That Drug(s)
Total Dogs)
Single-Arm Trials
Piroxicam a 94/76 9/11/16 3 18 59 20 120 244 3
Deracoxib a 26/24 4/11/15 0 17 71 12 133 323 54
Vinblastine a,g,h 28/28 11/21/28 0 36 50 14 122 147 58
Vinblastine–folate con- 10/9 10/40/40 0 56 44 0 58 115 66
jugate a
Vinblastine/toceranib/COX 10/9 20/0/20 0 33–55 i NA NA NA NA 27
inhibitor f
Mitoxantrone/piroxicam f 55/48 NA/NA/11 2 33 46 19 194 291 1
Carboplatin a 14/12 21/14/28 0 0 8 92 41 132 1
Carboplatin/piroxicam a 31/29 13/13/19 0 38 45 17 NA 161 1
Doxorubicin/piroxicam f 34/23 NA/NA/NA 0 9 60 30 103 168 55
Gemcitabine/piroxicam f 38/37 11/3/11 5 22 51 22 NA 230 57
Cisplatin (60 mg/m ) 18/16 NA/28/33 0 19 25 56 75 130 1–3
2 a
2 a
Cisplatin (40–50 mg/m ) 14/14 7/7/7 0 7 36 57 78 307 1–3
2
Cisplatin (60 mg/m )/ 14/12 14/14/28 0 50 17 33 NA 329 1–3
piroxicam a
2
Cisplatin (60 mg/m / 14/11 NA/NA/NA 0 27 73 0 NA 253 60
piroxicam/tavocept f
Chlorambucil (4 mg/m 30/30 10/30/33 0 3 67 30 119 221 61
2
daily) a
5-Azacitidine a 19/18 5/15/15 0 22 50 22 NA 203 67
Mitomycin C—intravesical a 13/12 0/0/0 0 42 58 0 120 223 69

a Diagnosis based on histopathology.
b When dogs receiving vinblastine alone failed, there was then the option for the dogs to receive piroxicam alone or other drugs. Twenty dogs received piroxicam alone after failing vinblastine alone. The
responses to piroxicam were 3 (15%) PR, 9 (45%) SD, 5 (25%) PD, and 3 (15%) NA. Twelve of these dogs received additional therapy after failing piroxicam. In the combined therapy arm, 15 dogs received
additional therapy after failing vinblastine/piroxicam.
c Dogs that initially received cisplatin alone and had tumor progression were then treated with piroxicam alone; two dogs had PR and five dogs had SD with piroxicam treatment. This could have contributed
to the favorable survival in that treatment arm.
d Despite favorable tumor response, the combination of cisplatin and piroxicam is not recommended for routine use because of frequent renal toxicity.
e After failing cisplatin alone, options were given for the dogs to receive firocoxib alone or other drugs. Thirteen dogs received firocoxib alone after failing cisplatin alone, and tumor responses included 2
PR, 4 SD, and 7 PD. This (and other drugs) could have contributed to the longer survival time.
f Study included dogs with cytologic evidence of TCC and dogs with biopsy-proven TCC.
2
h The majority of dogs had failed prior therapy before receiving vinblastine. The dosage of vinblastine used in this trial was 3 mg/m every 2 weeks. In most dogs in the trial, however, subsequent dose
2
reduction was necessary because of myelosuppression. The currently recommended starting dosage of vinblastine for dogs with iUC is 2.5 mg/m every 2 weeks for medium to large dogs and 2.0 mg/
2
m every 2 weeks for small dogs with subsequent dose escalation in the absence of toxicity.
i Seventeen of the dogs had failed a COX inhibitor before enrolling in the trial and continued to receive the COX inhibitor during the vinblastine treatment.
j In the study, the tumor masses were measured by ultrasound and by computed tomography. At 8 weeks, two different ultrasound operators reported tumor responses of 33% and 55% respectively.
More advanced TNM stage is associated with a poorer prognosis; the percentages of dogs with metastasis for each study are included.
CR, Complete remission; NA, information not available; PD, progressive disease; PFI, progression-free interval; PR, partial remission; SD, stable disease.

that sequentially receive multiple different treatment protocols Subsequent treatment changes are based on change in tumor size
over the course of their disease. Baseline measurements of the iUC and treatment tolerability. With this approach, iUC growth can be
masses are obtained, an initial treatment protocol is instituted, and controlled in approximately 75% to 80% of dogs, quality of life is
the iUC masses remeasured at 4- to 8-week intervals. The initial usually very good, and MSTs have extended well beyond a year. 1–3
treatment is continued as long as the iUC is controlled (PR, SD), Simultaneously combining multiple chemotherapy agents in dogs
side effects are acceptable, and quality of life is good. Clinical signs with iUC is not currently recommended because the benefit has
do not consistently follow changes in tumor size with therapy; thus not been determined, toxicity is likely to increase, and the potential
remeasuring the tumor is essential. If cancer progression or unac- development of resistance to multiple drugs at the same time could
ceptable toxicity occurs, then a different treatment is instituted. limit the options for subsequent therapy.