Carboplatin and radiation therapy. Carboplatin chemotherapy plus coarse fractionation radiation therapy evaluated in 11 cats was well-tolerated but only minimally effective.²⁴ While most owners were happy with their cats' quality of life, the few hospital visits, and the cost of this protocol, the median progression-free interval was only 119 days (range of 40 to 245 days) with a median survival time of 161 days.²⁴

Gemcitabine and radiation therapy. Gemcitabine is a pyrimidine analogue with a wide range of antitumor activity against solid tumors.²⁵ In one study, when given in low doses (25 mg/m² twice weekly) as an adjunctive chemotherapeutic agent to palliative radiation, gemcitabine exhibited potent radiosensitizing effects in vitro and in vivo.²⁵ Each of the eight patients in this study appeared to tolerate the multimodality treatment well with no exacerbation of presenting clinical signs and an overall response rate of 75%. Determination of responses was based on physical examination, thus the response rate may have been overestimated. Additionally, the median duration of remission was only 42.5 days (range 11 to 85 days), with a median survival time of 111.5 days (range 11 to 234 days).²⁵

In another study evaluating the efficacy and toxicity of gemcitabine when given with definitive radiation, 10 cats with oral squamous cell carcinoma were treated with the same gemcitabine dosage (25 mg/m² twice weekly) in conjunction with radiation given in 3-Gy fractions Monday through Friday with the intent to give a total of 19 fractions.²⁶ Six cats did not complete the radiation course because of local normal tissue toxicosis (e.g. mucositis). Four cats required chemotherapy dose reduction or delay because of unexpected hematologic toxicosis, while two cats had reduction or delay because of other concerns such as inappetence, increased renal values, or anemia.²⁶ The degree of myelosuppression these patients experienced considering the insignificant volume of bone marrow irradiated was surprising, thus the cause of the toxicosis was unclear. Additionally, the antitumor effect was poor, with a median local control time of three months. The degree of toxicosis was such that the authors did not recommend further investigation of this protocol.²⁶

One study evaluated four different treatments in 52 cats with oral squamous cell carcinoma: seven cats were treated with surgery alone, 24 with definitive radiation therapy, 11 with radiation therapy combined with chemotherapy, and 10 with radiation therapy combined with local hyperthermia.⁵ Radiation was given in 10 to 12 4-Gy fractions on a Monday-Wednesday-Friday schedule. Chemotherapy was low-dose cisplatin (7.5 to 10 mg/m² intravenously given Monday and Friday), used as a radiosensitizer; no increased toxicosis was seen. Survival times ranged from one to 15 months; the overall median survival time was two months. Cats treated with surgery alone had a median survival time of one and a half months, compared with a median of three months for radiation alone, two and a half months for radiation plus chemotherapy, and two and a half months for radiation plus hyperthermia. No difference in survival rates was found among the treatments. Overall survival of the cats in this particular study was poor, and because of the potentially fatal effects of cisplatin in cats, it is not a recommended treatment option.⁵

The longest survival time reported to date in cats with oral squamous cell carcinoma was in a small study of seven cats treated with mandibulectomy and adjuvant full-course radiation therapy (five orthovoltage, one cobalt, one combined). All of the cats were stage III, as their tumors were > 4 cm in diameter; one cat had ipsilateral lymph node metastasis. All cats had a gastrostomy tube placed at the time of surgery; the duration of tube usage ranged from three to 44 days (median 15 days). All cats developed mild to moderate tongue lagging postoperatively, and drooling and messy eating were long-term complications. Owners usually bathed their cats' chests and feet at least once a day. No comment was made about owner satisfaction with the procedure. Despite multimodality therapy, six of the seven cats still developed local recurrence, with a median disease-free interval of 11 months. The overall median survival time in this small study was 14 months.⁴ This survival time is quite lengthy in cats with stage III disease and provides support for further investigation of the use of curative-intent radiation therapy after mandibulectomy for oral squamous cell carcinoma.

Other treatment options

Cyclooxygenase (COX) enzymes catalyze the synthesis of prostaglandins and exist as two isoforms, COX-1 and COX-2. COX-2 is a strong mediator of inflammation and is upregulated in numerous human tumors. An immunohistochemical study looked at COX-2 expression in various feline neoplasms to determine whether COX inhibition may be a potential target for prevention or treatment of tumors in cats.²⁷ COX-2 was found in only 9% of feline oral squamous cell carcinomas and none of the cutaneous squamous cell carcinomas. The absence of COX-2 expression suggests that COX-2 inhibitors will likely have a low potential as an anticancer agent for this tumor type.²⁷

A new strategy emerging in the treatment of cancer is administering agents directed against components of pathways involved in cancer progression. Combining these drugs with conventional treatments such as radiation therapy and chemotherapy may lead to improved outcomes. These drugs include tyrosine kinase inhibitors, some of which are directed against the epidermal growth factor receptor (EGFR). EGFR overexpression has been found in 80% to 90% of human head and neck carcinomas and recently was shown to be expressed in 70% of feline oral squamous cell carcinomas.²⁸ Altered EGFR expression may play a role in feline oral squamous cell carcinoma and provides a rationale for possible benefit of EGFR inhibitors in these patients.