While surgical and radiation treatment options are helpful in controlling local disease, they offer no benefit in the control
of metastatic disease. Tumors associated with high metastatic potential, including oral melanoma and tonsillar squamous cell
carcinoma, need an adjuvant form of therapy to increase the overall survival time. As fibrosarcomas are rarely metastatic
and tend to be chemotherapy-resistant, chemotherapy does not generally play a role in their management.
Melanoma. Chemotherapy has, in general, been considered ineffective against oral melanoma. The most common chemotherapeutic agent
used to treat dogs with melanoma is carboplatin. In a study evaluating 25 dogs with measurable melanomas treated with 300
to 350 mg/m2 carboplatin, an overall response rate of 28% (7/25) was seen, with one complete remission and six partial remissions.46 Twenty of the 25 (80%) dogs had stage III or IV disease. The reported response to carboplatin in dogs with macroscopic disease
provides support for the integration of this chemotherapy drug in treating dogs with microscopic disease.
A second study evaluating the MST of dogs treated for oral melanoma without radiographic evidence of pulmonary metastases
with four weekly fractions of 9 Gy radiation alone vs. radiation and carboplatin showed no significant difference in survival
time with the addition of carboplatin. The MST for dogs treated with radiation alone was 10 months with 10 of 13 (77%) experiencing
measurable tumor response. The MST for dogs treated with both radiation and carboplatin was 9.5 months with 13 of 15 (87%)
experiencing measurable tumor response.14 Overall, the carboplatin was well-tolerated and resulted in no treatment discontinuations or death. While no clear benefit
was seen with carboplatin in dogs with macroscopic disease, the number of dogs in this retrospective study was low, warranting
further studies in dogs with microscopic disease.
In 11 dogs treated with cisplatin (50 to 55 mg/m2 ) and piroxicam (0.3 mg/kg once daily) for oral melanoma, two experienced complete remissions for an overall response rate
of 18%.47 Seven of 17 dogs treated either for melanoma or squamous cell carcinoma with this protocol developed renal toxicosis, mostly
mild to moderate.47 However, in an earlier study of dogs treated with a combination of cisplatin (60 mg/m2 every 21 days) and piroxicam (0.3 mg/kg once daily) for transitional cell carcinoma of the bladder, 12 of 14 dogs developed
renal toxicosis, with nine of the dogs having moderate to severe toxicosis.48 The severity of the renal effects in this group of dogs may relate to the slightly increased dose of cisplatin given or
the primary cancer being associated with the urinary tract. Regardless, at this time, this combination of drugs is not recommended.
Squamous cell carcinoma. Systemic therapy may be indicated as sole or adjuvant therapy for nonresectable squamous cell carcinoma and tonsillar squamous
cell carcinoma. In one study evaluating 17 dogs with bulky squamous cell carcinoma of any oral location treated with piroxicam
alone, the overall remission rate was 18%, with one complete remission and two partial remissions.49 In nine dogs with squamous cell carcinoma, two experienced a complete remission and three had partial remissions when treated
with cisplatin and piroxicam for an overall remission rate of 55.5%.47 However, concerns with the nephrotoxicity of this protocol (see above) limit its use. An additional study evaluated carboplatin and piroxicam in seven dogs with nontonsillar squamous cell carcinoma
and showed complete clinical remission in five of seven (71%) dogs, with a MST of 19.2 months.50 Further study of this potentially promising combination is warranted.
An earlier study of 22 dogs with tonsillar squamous cell carcinoma compared surgery with chemotherapy (three different protocols,
none of which included piroxicam) to surgery, chemotherapy, and radiation. Survival times for the first group ranged from
two to four months compared with nine months for tri-modality therapy.28 Chemotherapy with carboplatin and piroxicam, with and without radiation therapy, to treat dogs with tonsillar squamous cell
carcinoma should be explored.