By using flow cytometry, a retrospective analysis of the DNA content of 40 primary canine mast cell tumors and seven lymph nodes that contained metastatic mast cell tumor from 44 dogs of various breed, sex, and age was performed on formalin-fixed, paraffin-embedded samples of the tumors and nodes. These samples were chosen according to the following criteria: samples contained sufficient well-preserved tumor tissue in the paraffin block for processing, sufficient patient history data were available, clean and homogeneous cell suspensions were obtained after processing, and interpretable DNA histograms were produced on analysis. The ploidy data obtained were compared with the histopathologic grade, the anatomical site of occurrence, the clinical stage of the tumors, and the survival of the dogs. Over 70% (29/40) of the mast cell tumors were diploid. Three metastatic mast cell tumors in lymph nodes had the same ploidy status as their corresponding primary tumors. In five dogs, mast cell tumors from multiple sites in each dog displayed similar ploidy status. Of 26 dogs evaluated for survival times, 69% (18/26) had diploid tumors and 31% (8/26) had aneuploid tumors. When numbers of diploid versus aneuploid tumors were compared, no significant difference was found between any two grades, clinical stages, or anatomic sites. A significant difference (P = 0.02) was found, however, between aneuploid and diploid tumors when comparing Stage I and non-Stage I disease. The Kaplan-Meier survival plot indicated a tendency towards an increased survival within the first year in dogs with diploid versus aneuploid tumors (P = 0.06).

Squamous cell carcinoma (SCC) accounts for approximately 10% of all feline tumors. The purpose of this retrospective study was to describe outcomes for a group of cats with oral SCC that were treated with palliative radiation therapy. Fifty-four cats met the inclusion criteria of nonresectable, oral SCC treated with coarse fractionated megavoltage (MeV) radiation therapy. Radiation therapy for all cats was delivered with a 6 MeV linear accelerator. Total radiation doses of 24 Gray to 40 Gray were administered in three to four fractions, once-per-week over 4 to 5 weeks. Concurrent chemotherapy protocols varied and were administered at the discretion of the clinician and client. Forty-nine patients completed the planned treatment protocols. Overall mean and median survival times for cats completing the planned treatment protocols were 127 and 92 days (n = 49). Mean and median survival times of cats receiving palliative radiation therapy alone were 157 and 113 days (n = 12). Mean and median survival times of patients receiving both radiation therapy and chemotherapy were 116 and 80 days (n = 37). Patients with sublingual tumors had a median survival time of 135 days (n = 15), compared to mandibular tumors that had a median survival time of 80 days (n = 26). For the majority of patients that completed the planned treatment protocol (65%), owners reported a subjectively improved quality of life. Findings from this uncontrolled study supported the use of palliative radiation therapy for cats with nonresectable oral squamous cell carcinoma.

An inexpensive combination chemotherapy protocol containing cyclophosphamide, dactinomycin, and 5-fluorouracil was evaluated in dogs with carcinomas. Fifteen dogs were entered in this study, and there were 1 complete response and 2 partial responses among 1 2 evaluable dogs.However, 6 of 1 5 dogs (40%) developed neurotoxicity. The neurotoxicity of this protocol was compared with a previactinomycin (actinomycin D; Cosmegen, Merck, D Sharp and Dohme Research Laboratories), a potent inhibitor of protein and RNA synthesis, has recently been shown to have a broad spectrum of antineoplastic activity against spontaneous tumors in dogs.' Dactinomycin is inexpensive when compared with other commonly used antineoplastic agents (eg, doxorubicin, mitoxantrone, cisplatin, bleomycin), and this is a desirable factor in a veterinary oncology practice. Therefore, we designed an inexpensive chemotherapy protocol using cyclophosphamide (Cytoxan; Mead Johnson and Company, Evansville, IN), dactinomycin (Cosmegen; Merck, Sharp and Dohme, West Point, PA), and 5-fluorouracil (Fluorouracil; Roche Laboratories, Nutley, NJ) (CDF) for dogs with carcinomas or adenocarcinomas.In addition to being efficacious and inexpensive, chemotherapy protocols designed for widespread use in veterinary medicine must be relatively safe and nontoxic. Use of dactinomycin has resulted primarily in gastrointestinal toxicity in approximately 30% of the dogs treated; myelosuppression was rare.' Cyclophosphamide may cause myelosuppression, nausea and vomiting, hemorrhagic cystitis, and, at high doses, cardiac toxicity.'" 5-Fluorouracil(5-FTJ) has been associated with neurotoxicity, mucositis, and myelosuppression.'-IO The CDF protocol was evaluated for toxicity and compared with a similar 5-FLJ-containing protocol previously used at the Veterinary Teaching Hospital-Ohio State University (VTH-OSU). Materials and Methods Eligibility CriteriaDogs with biopsy-proven carcinomas or adenocarcinomas were eligible for this study. Criteria for entry included an expected survival greater than 3 weeks, a packed cell volume (PCV) greater than 18%, a neutrophil count greater than 2,000 cells/pL, and a platelet count greater than 50,000 cells/pL. In addition, the dogs could not have received any chemotherapy for the previous 2 weeks, nor could they have received prior dactinomycin chemotherapy. Chemotherapy ProtocolThe tumors were staged according to the Worth Health Organization-TNM system," and the dogs were treated as outlined in Table 1. A total of 10 cycles or 3 cycles beyond a complete response were to be given. Withdrawal from the study was based on prcgressive disease, unacceptable toxicity, or the owner's request. Toxicity Monitoring and Response CriteriaComplete blood counts (CBC) were evaluated weekly; hematclogical, gastrointestinal, and neurological toxicity were graded according to Table 2. Tumor responses were evaluated every 3 weeks and recorded as complete response (CR), disappearance of all clinically detectable disease; partial response (PR), >50% decrease ...

Its cytotoxic mechanism of action is believed to be DNA intercalation and inhibition of RNA and protein synthesis. This drug has been used to successfully treat Wilms' tumor, rhabdomyosarcoma, choriocarcinoma, testicular carcinoma, and Ewing's sarcoma in humans2Actinomycin D has received limited use in veterinary medicine. Three of 4 dogs with lymphoma experienced short-lived responses when treated with a dose of 0.025 mgJkg/wk IV.3 Actinomycin D (0.015 mgJkg/d for 5 days) was also used as an adjuvant treatment to surgery and radiotherapy in a dog with an atypical nephroblastoma; however, it caused pancytopenia and diarrhea in this dog: Actinomycin D (0.5 mdm2 weekly) was also used in combination with chlorambucil (2 ms/m2 orally 4 days a week) in a dog with metastatic seminoma, but neither toxicity nor response were rep~rted.~ Actinomycin D is inexpensive when compared with other antineoplastic agents (eg, doxorubicin, cisplatin, bleomycin, mitoxantrone) but has not been extensively used in veterinary medicine due to its previously reported toxicity in dogs.6-8 Doses of actinomycin D in these studies ranged from 0.6 mg/m2 to 6 mg/m2, and single doses greater than 1.5 to 2.0 mg/m2 were frequently fatal. The drug's main side effects were severe m yelosuppression and gastrointestinal toxicity.The purpose of this study was to perform a preliminary clinical evaluation of the antineoplastic effects and toxicity of actinomycin D in dogs with measurable tumors. This study was designed to determine not the maximum tolerated dose of actinomycin D, but rather the response and toxicity at doses that were at the lower range of previous pharmacological studies. Materials and Methods Patient PopulationEligibility criteria for entry into this study included histopathologically or cytologically diagnosed malignancy, presence of mea- Treatment ProtocolActinomycin D, reconstituted in sterile water and diluted to 3 to 5 mL in normal saline solution, was administered IV every 3 weeks through a butterfly catheter over 5 minutes. The initial dose of0.5 mg/m2 was increased by 0. I mg/m2 for each treatment until toxicity was observed; treatment was then continued at the next lower dose not associated with toxicity. Refemng veterinarians were permitted to administer every other dose for convenience to the client, but no dose escalation was performed by them. Treatments were continued until no further response was noted, progressive disease was observed, or a total of 8 treatments were administered. Tumor response was evaluated by us. Maximum doses of actinomycin D and number of doses were recorded. Evaluation of Toxicity and ResponseComplete blood counts and platelet counts were performed by the clinical pathology laboratory at the Veterinary Teaching Hospital-Ohio State University (VTH-OSU) or by the referring veterinarian using a commercial veterinary laboratory supervised by a veterinary clinical pathologist prior to each dose and I week after each injection of actinomycin D. The hematologic toxicity was graded according to the para...

Circulating N-terminal PTH-related protein (PTHrP), N-terminal PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in normal dogs and dogs with cancer-associated hypercalcemia (CAH), parathyroid adenomas, and miscellaneous tumors. PTHrP was undetectable (less than 1.8 pM) in normal dogs and increased in dogs with CAH due to adenocarcinomas derived from apocrine glands of the anal sac (44.9 +/- 27 pM), lymphoma (8.3 +/- 4.4 pM), and miscellaneous carcinomas (13.3 +/- 11.4 pM). The PTHrP concentration decreased in dogs with lymphoma and anal sac adenocarcinomas after successful treatment of CAH. The PTHrP concentration had a significant linear correlation with total serum calcium in dogs with anal sac adenocarcinomas and hypercalcemia, but not in dogs with lymphoma and hypercalcemia. Serum N-terminal PTH concentrations were usually in the normal range (12-34 pg/ml) for all groups of dogs except dogs with parathyroid adenomas (83 +/- 38 pg/ml). The serum PTH concentration increased after successful treatment of CAH. Serum 1,25-(OH)2D concentrations were decreased, normal, or increased in dogs with CAH, and 1,25-(OH)2D levels decreased after treatment of CAH. In summary, circulating concentrations of PTHrP are consistently increased in dogs with CAH, and PTHrP appears to play an important role in the induction of hypercalcemia.