Published results can be found here.

Study Start Date: 12/01/2006
Study End Date: 04/01/2008

Treatment of Feline Oral Squamous Cell Carcinoma (SCC) with 2-Difluoromethylornithine (DFMO)

Oral squamous cell carcinoma is an aggressive cancer that accounts for approximately 70% of oral tumors in cats (Harvey and Emily, 1993). Optimal long term results of therapy for this type of feline cancer can rarely be achieved by current therapies (Ogilvie and Moore, 2001). Although surgical excision is the treatment of choice for resectable tumors, pet owners rarely notice clinical signs of disease until the tumor is already too large. Long term results of treatment with either surgery, chemotherapy or radiation treatment have been frustrating, with most cats dying within 6 months of the diagnosis. This study is designed to use a new treatment for feline squamous cell carcinoma which has shown great promise in treatment of squamous cell carcinoma in mice. Given orally to mice with squamous cell carcinoma, 2-difluoromethylornithine (DFMO) has achieved complete responses and apparent cures in a high percentage of mice. This treatment will be offered to clients whose pets are not good candidates for surgical resection and/or clients who opt to pursue nonsurgical treatment. Enzyme activity and polyamine levels will be assessed in tumor tissue, adjacent normal tissue, serum and urine at 0 weeks and 8 week post treatment.

Study Design:
Prospective, unblinded, un-controlled.

Sample Size:
14

Inclusion criteria:

1. Patients must be deemed to be in otherwise acceptable systemic health based on results of physical examination, complete blood count, serum chemistry screen, urinalysis and serum thyroid (T4) hormone level performed at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania (MJR-VHUP).
2. Thoracic radiographs, head CT scan, dental radiographs, mandibular lymph node aspirate, incisional biopsy of the lesion (confirming the diagnosis of SCC) and normal tissue away from the lesion, and brainstem auditory evoked response test (BAER) will be performed. This information will be used to determine the severity of disease. Patients may be excluded from the study if tests show signs of spread of oral SCC to regional or distant sites. Patients may also be excluded from the study if the severity of the oral tumor is already so great that quality of life has already been significantly affected.
3. In cases where tumors are of a resectable size, surgery will be presented as the treatment of choice. DFMO therapy will be offered as an option to clients who choose not to pursue other methods of treatment, including surgery, radiation or other chemotherapy options.
4. Clients must agree to return to MJR-VHUP for regular monitoring and repeat blood work and urine tests, including a possible anesthetic reexamination 8 weeks after the start of therapy, which may include oral examination, dental radiographs, tumor measurement, biopsy, photographs, CT scan and BAER test at that time, and necropsy after the patient dies or is euthanized. Post-treatment samples will be obtained immediately postmortem if for any reason the patient must be euthanatized prior to the 8 week recheck.
5. Consent form must be signed by pet owner. Patients deemed acceptable candidates based on initial physical examination will be admitted to the hospital for preoperative evaluation, including physical examination, complete blood count, serum chemistry screen, urinalysis and serum thyroid (T4) hormone level, FeLV and FIV ELISA tests, and thoracic radiographs. In those patients whose preoperative tests are favorable for inclusion, anesthesia will be induced to perform oral examination, dental radiographs, head CT scan, measurements and photographs of the lesion, mandibular lymph node aspirates, brainstem auditory evoked response test (BAER), and biopsy of the lesion and tissue adjacent to the lesion. Patients who meet all criteria and whose biopsies are histologically confirmed as SCC will begin DFMO therapy as part of a phase I/II study consisting of a dose escalation regimen.

Exclusion Criteria:
Patients with concurrent medical disease which may preclude completion of the study (significant anorexia), or that may make difficult the interpretation of tolerability (e.g. history of prior vomiting) or efficacy (e.g presence of widespread or concurrent neoplasia not confined to the oral cavity) of the drug. Exclusion will be at the discretion of the primary investigator based on the candidate's overall results of the pre-screening history and diagnostics.

Study Controls:
n/a

Costs/Reimbursements:
The cost of diagnostics and treatment is greatly reduced, but the clients of cats already diagnosed with oral SCC are responsible for an initial monetary input of $454 which includes DFMO, anesthesia and diagnostics associated with the 0 and 8 week visit. Every two weeks, a complete blood count and chemistry screen is to be done at the client's expense. A necropsy will be performed at no charge to the client at the time of death or euthanasia.

Full Disclosure information:

• The study is funded by an Institutional (university intramural) grant.
• The investigators do not have any conflict of interest.
• The study will be published if results are negative.
• The study will be reported on VIN.
• The authors will acknowledge VIN if the study is published.