Treatment of MRI-Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dogs.

BACKGROUND: Stereotactic radiotherapy (SRT) is an emerging technique for treating tumors in animals. OBJECTIVES: To assess the outcome of dogs with suspected intracranial trigeminal nerve peripheral nerve sheath tumors (PNST) treated with SRT. ANIMALS: Eight dogs with presumptive PNST. METHODS: This was a retrospective study of dogs identified by searching UC Davis Veterinary Medical Teaching Hospital medical records for dogs treated with SRT for a presumed PNST. Presumptive diagnosis was based on magnetic resonance imaging. SRT was delivered in 3 dose fractions of 8 Gray (Gy) on consecutive days or every other day to a total dose of 24 Gy. RESULTS: Median disease-specific survival was 745 days (range: 99-1375 days, n = 6). No signs of acute adverse effects of radiation treatment were recorded. Late radiation effects versus tumor progression could not be confirmed histopathologically because of few animals undergoing necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides preliminary evidence that dogs with PNST benefit from SRT in terms of long-term survival. The treatment appears to be well tolerated and requires fewer anesthetic events for animals compared to full-course radiation.

A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy in tumor-bearing equidae.

BACKGROUND: The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. OBJECTIVES: To provide preliminary evidence of the efficacy of doxorubicin in tumor-bearing horses, explore drug pharmacokinetics profile, and estimate period of risk of exposure to drug residues. ANIMALS: Twelve horses with 37 tumors. PROCEDURES: Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m(2) and 4 horses received 4 of 6 treatment cycles at 70 mg/m(2) . Clinical signs, tumor responses, and toxicoses were evaluated. Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m(2) by high-performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine). RESULTS: Thirty tumors, including lymphomas, carcinomas, sarcoids, and melanoma, were evaluated for efficacy. The overall response rate was 47% (95% CI, 28-65%). Doxorubicin was not found to be effective against melanomas. Lymphomas and carcinomas were most responsive. Pooled serum Cmax and half-life of doxorubicin were 121.3 ng/mL and 12.9 hours, respectively. There were no detectable residues in fecal samples up to 3 weeks after treatment and in plasma and urine after 2 and 3 days, respectively. CONCLUSION AND CLINICAL RELEVANCE: This study provides preliminary evidence that single-agent doxorubicin at a dosage of 70 mg/m(2) has a broad spectrum of activity. The risk of exposure to drug residues in plasma and feces was low. Direct contact with urine-contaminated wastes should be avoided for 2 days after treatment.

Phase I dose escalation of doxorubicin chemotherapy in tumor-bearing equidae.

BACKGROUND: There is no information on the use of doxorubicin in horses with tumors. OBJECTIVE: To determine dose-limiting toxicosis (DLT) and maximum tolerated dose (MTD) of doxorubicin in tumor-bearing horses. ANIMALS: Seventeen horses with 34 localized or multicentric advanced tumors. METHODS: Two-stage dose-ranging design involving intrapatient and interpatient dose escalation. Treatment protocol included 6 treatment cycles given at 3-week intervals with dosages ranging from 40 to 85 mg/m(2). Clinical signs, hematologic, and nonhematologic changes were evaluated. RESULTS: Total doses ranged from 1,127 to 2,900 mg in 12 horses that completed the assigned treatment protocols. The MTD was 75 mg/m(2). Hypersensitivity reactions and neutropenia were dose limiting. Hypersensitivity was dose-dependent but schedule invariant. Neutropenia was dose- and cycle-dependent but dose-escalation schedule invariant. Cardiotoxicity was not observed. CONCLUSION AND CLINICAL RELEVANCE: The recommended dosage of doxorubicin to treat horses is 70 mg/m(2) given at 3-week intervals as single agent. Adjunctive treatment with antihistamines and nonsteroidal anti-inflammatory drugs is recommended to control hypersensitivity.

Sequential low-dose rate half-body irradiation and chemotherapy for the treatment of canine multicentric lymphoma.

BACKGROUND: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels. HYPOTHESIS: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs. ANIMALS: Thirty-eight client-owned animals diagnosed with multicentric lymphoma. METHODS: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy. RESULTS: The median 1st remission was 410 days (95% confidence interval [CI] 241-803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334-1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.

A toxicity study of low-dose rate half-body irradiation and chemotherapy in dogs with lymphoma.

Thirteen dogs with previously untreated multicentric lymphoma were enrolled in a prospective study investigating the effects of low-dose rate total body irradiation (TBI) and chemotherapy. Dogs received either 6 or 8 Gy TBI in half-body fractions, 2 weeks apart. Toxicity consisted of mild to moderate haematological and gastrointestinal (GI) signs. One dog died from treatment complications. Anorexia was noted independent of dose. Haematological toxicity was more common and more severe after 8 Gy treatment. GI toxicity was more likely postcaudal half-body irradiation with 8 Gy. Other than leukotrichia, late effects from radiation were not observed. Results indicated that haematological and nonhaematological toxicity was dose dependent. However, the protocol was well tolerated and treatment intensification using a 2-week inter-radiation interval was possible in all dogs treated with 6 Gy. Preliminary survival data for these dogs were very encouraging, providing a strong rationale to analyse the efficacy of low-dose rate irradiation (LDRI) in canine lymphoma.

Expression of a transforming gene (E5) of bovine papillomavirus in sarcoids obtained from horses.

OBJECTIVE: To determine expression of a transforming gene (E5) of bovine papillomavirus in sarcoids, other tumors, and normal skin samples collected from horses with and without sarcoids. SAMPLE POPULATION: 23 sarcoids and 6 samples of normal skin obtained from 16 horses with sarcoids, 2 samples of normal skin and 2 papillomas obtained from horses without sarcoids, and 1 papilloma obtained from a cow. PROCEDURE: Protein was extracted from tissue samples collected from horses and incubated with agarose beads covalently coupled to Staphylococcus aureus protein A and an anti-E5 polyclonal antibody. Following incubation, proteins were eluted from the beads and electrophoresed on a 14% polyacrylamide gel and transferred to a polyvinylidene difluoride membrane. The E5 protein was detected by use of western blot analysis, using a chemiluminescence detection system. RESULTS: All 23 sarcoids had positive results for expression of E5 protein. Quantity of viral protein appeared to vary among sarcoids. All other tissues examined had negative results for E5 protein. Highest expression for E5 protein was observed in biologically aggressive fibroblastic variants of sarcoids, compared with expression in quiescent tumors. CONCLUSIONS AND CLINICAL RELEVANCE: This study documented that activation and expression of the E5 gene is evident in sarcoids obtained from horses. These data support the conclusion that infection with bovine papillomavirus is important in the initiation or progression of sarcoids in horses. Treatment strategies designed to increase immune recognition of virally infected cells are warranted.

Bovine papillomavirus DNA in neoplastic and nonneoplastic tissues obtained from horses with and without sarcoids in the western United States.

OBJECTIVE: To determine the incidence of bovine papillomavirus (BPV) type 1 or 2 in sarcoids and other samples of cutaneous tissues collected from horses in the western United States. ANIMALS: 55 horses with sarcoids and 12 horses without sarcoids. PROCEDURE: Tissue samples (tumor and normal skin from horses with sarcoids and normal skin, papillomas, and nonsarcoid cutaneous neoplasms from horses without sarcoids) were collected. Tissue samples were analyzed for BPV-1 or -2 DNA, using a polymerase chain reaction (PCR) and restriction fragment length polymorphism. The PCR products from 7 sarcoid-affected horses were sequenced to evaluate percentage homology with expected sequences for BPV-1 or-2. RESULTS: Most (94/96, 98%) sarcoids contained BPV DNA. Sixty-two percent of the tumors examined had restriction enzyme patterns consistent with BPV-2. Thirty-one of 49 (63%) samples of normal skin obtained from horses with sarcoids contained BPV DNA. All samples subsequently sequenced had 100% homology with the expected sequences for the specific viral type. All tissues from healthy horses, nonsarcoid neoplasms, and papillomas were negative for BPV DNA. CONCLUSIONS AND CLINICAL RELEVANCE: Bovine papillomaviral DNA was detected in essentially all sarcoids examined. There appears to be regional variation in the prevalence of viral types in these tumors. The fact that we detected viral DNA in normal skin samples from horses with sarcoids suggests the possibility of a latent viral phase. Viral latency may be 1 explanation for the high rate of recurrence following surgical excision of sarcoids.

Equine basal cell tumors: 6 cases (1985-1999).

Basal cell tumors are rare benign tumors in horses. Over a 15-year period, 6 horses were diagnosed with basal cell tumors. The tumors were well-circumscribed. freely moveable, firm, raised papules, nodules, or masses that ranged from 0.6 to 5 cm in diameter. Five of the 6 tumors were ulcerated. Based on gross appearance, the tumors were diagnosed as sarcoids, and 1 was diagnosed as a melanoma. The range of age of affected horses was 6-26 years. The tumors were identified clinically 1 week to 3 years before excision. In 4 horses for which information was available, complete surgical excision was curative with no recurrence 4 months to 2 years after removal.

Prognostic factors and patterns of treatment failure in dogs with unresectable differentiated thyroid carcinomas treated with megavoltage irradiation.

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with unresectable thyroid carcinomas treated with definitive megavoltage irradiation and analyze prognostic factors of PFS and patterns of failure (local recurrence vs metastasis). DESIGN: Prospective clinical trial. ANIMALS: 25 dogs with locally advanced thyroid carcinomas and no evidence of metastasis. PROCEDURE: Dogs were treated with 48 Gy during 4 weeks on an alternate-day schedule of 4 Gy/fraction. RESULTS: Irradiation was safe and effective for treatment of large unresectable thyroid carcinomas. Progression-free survival rates were 80% at 1 year and 72% at 3 years. Time to maximum tumor size reduction ranged from 8 to 22 months. Factors affecting PFS were not found. Twenty-eight percent (7/25) of dogs developed metastasis. Dogs with bilateral tumors had 16 times the risk of developing metastases, compared with dogs with a single tumor. Dogs with no evidence of tumor progression had 15 times less risk of developing metastases. Radiation-induced hypothyroidism was suspected in 2 dogs 13 and 29 months after irradiation. CONCLUSIONS AND CLINICAL RELEVANCE: Irradiation is effective for local control of thyroid tumors, despite their slow regression rate. Results provided evidence that local tumor control affects metastatic outcome in dogs with thyroid carcinomas and is a strong basis for the development of new approaches that include irradiation in the management of dogs with advanced thyroid carcinomas. Improvements in local tumor control alone may be insufficient to improve survival times because of the high risk of metastatic spread before an initial diagnosis is made, which warrants initiation of early systemic treatment.

Influence of tumor cell proliferation and sex-hormone receptors on effectiveness of radiation therapy for dogs with incompletely resected meningiomas.

OBJECTIVE: To assess the influence of tumor cell proliferation and sex-hormone receptors on the efficacy of megavoltage irradiation for dogs with incompletely resected meningiomas. DESIGN: Longitudinal clinical trial. ANIMALS: 20 dogs with incompletely resected intracranial meningiomas. PROCEDURE: Dogs were treated with 48 Gy of radiation administered 3 times per week on an alternate-day schedule of 4 Gy/fraction for 4 weeks, using bilateral parallel-opposed fields. RESULTS: Tumor proliferative fraction measured by immunohistochemical detection of proliferating cell nuclear antigen (PFPCNA index) ranged from 10 to 42% (median, 24%). Progesterone receptor immunoreactivity was detected in 70% of tumors. Estrogen receptor immunoreactivity was not detected. An inverse correlation was found between detection of progesterone receptors and the PFPCNA index. The overall 2-year progression-free survival (PFS) rate was 68%. The only prognostic factor that significantly affected PFS rate was the PFPCNA index. The 2-year PFS was 42% for tumors with a high PFPCNA index (value > or = 24%) and 91% for tumors with a low PFPCNA index (value < 24%). Tumors with a high PFPCNA index were 9.1 times as likely to recur as were tumors with a low PFPCNA index. CONCLUSIONS AND CLINICAL RELEVANCE: This study confirms the value of irradiation for dogs with incompletely resected meningiomas. Prognostic value of the PFPCNA index suggests-that duration of treatment and interval from surgery to start of irradiation may affect outcome. Loss of progesterone receptors in some tumors may be responsible for an increase in PFPCNA index and may indirectly affect prognosis after radiation therapy.

Effects of glutamine supplementation of an amino acid-based purified diet on intestinal mucosal integrity in cats with methotrexate-induced enteritis.

OBJECTIVE: To determine effects of glutamine-supplemented and glutamine-free amino acid-based purified diets, compared with a dry expanded diet, on intestinal structure and function in a model that used cats with methotrexate-induced enteritis. ANIMALS: 18 adult specific-pathogen-free cats. PROCEDURE: 12 cats were given intragastric feedings of an amino acid-based purified diet supplemented with glutamine (7% [wt:wt]) or an isonitrogenous amount of glycine and alanine; 6 cats consumed a dry expanded diet. After 21 days, cats received methotrexate (MTX; 11 mg/kg of body weight, IV). Intestinal permeability testing was performed immediately before and 66 hours after MTX administration. Celiotomy was performed 72 hours after MTX administration for aseptic removal of mesenteric lymph nodes, collection of full-thickness intestinal biopsy specimens, determination of intestinal cellular proliferation, and collection of aortic and portal venous blood samples for determination of arteriovenous amino acid concentrations across the intestine. RESULTS: Administration of MTX was associated with severe enterotoxicosis manifested as diarrhea (8/12 cats), vomiting (12/12), and positive results for bacterial culture of mesenteric lymph nodes (12/12) in cats receiving the purified diets, independent of glutamine supplementation. Diet did not affect villus tip length and villus surface area in the small intestine or cellular proliferation. Administration of MTX was associated with significantly increased intestinal permeability, which was not attenuated by glutamine supplementation. CONCLUSIONS: Feeding of a glutamine-supplemented amino acid-based purified diet was unable to preserve intestinal function in cats with MTX-induced enteritis. CLINICAL RELEVANCE: Intestinal morphologic alterations correlate poorly with intestinal function as measured by means of bacterial translocation and intestinal permeability.

Lymph node uptake of interstitially delivered particulate contrast media before and after irradiation in dogs.

RATIONALE AND OBJECTIVES: The authors' purpose was to assess the effects of ionizing radiation on the uptake and distribution of interstitially delivered particulate contrast medium in normal lymph nodes in dogs. MATERIALS AND METHODS: Two milliliters of an iodinated nanoparticle suspension (NC 67722 Sterile Suspension, 76 mg of iodine per milliliter) was injected subcutaneously or submucosally into nine normal adult beagle dogs. Targeted lymph node groups were evaluated with computed tomography (CT). Region-of-interest analysis was used to estimate volume, attenuation, and iodine concentration of the opacified nodes and nonopacified contralateral nodes on CT images obtained before and 24 hours after the injection. All right-sided and some left-sided lymph nodes were irradiated with 50 Gy in 25 fractions of 2 Gy per day, beginning 28-35 days after the CT examination. Contrast medium administration and quantitative CT imaging were performed again 3 months after irradiation. RESULTS: Contrast material uptake resulted in a twofold increase in node volume before irradiation (P < .0001). Mean attenuation of contrast-enhanced nodes increased to 230-330 HU from a precontrast enhancement value of 36.5 HU. After irradiation, opacified node volumes decreased to approximately 25%-50% of their preirradiation volumes (P < .02). Contrast material uptake decreased 10%-15% after irradiation but was not significantly less than preirradiation uptake. Qualitatively, no substantial difference in contrast material distribution existed between irradiated and nonirradiated nodes. CONCLUSION: An elective irradiation dose decreased lymph node size, but the imaging characteristics of opacification were not otherwise appreciably altered 3 months after irradiation.

Comparison of perioperative versus postoperative intratumoral administration of cisplatin for treatment of cutaneous sarcoids and squamous cell carcinomas in horses.

OBJECTIVE: To determine the benefits of reducing the interval between surgical cytoreduction and intratumoral administration of cisplatin. DESIGN: Randomized clinical study. ANIMALS: 70 horses with 89 incompletely resected T2- and T3-stage sarcoids (n = 64) and squamous cell carcinomas (25). PROCEDURE: Horses were given 4 intratumoral treatments of cisplatin at 2-week intervals. The first treatment was given at the time of, or immediately after, surgical resection for horses treated in accordance with the perioperative protocol (group 1). Horses in group 2 were treated with cisplatin after the skin healed following surgical resection in accordance with the postoperative protocol. RESULTS: A difference was not found in duration of overall local tumor control between the 2 groups. Patterns of treatment failures and interval to failure differed between the 2 groups. Length of the surgical scar was the only factor that affected prognosis; an increase in length was associated with a poorer prognosis. A detrimental effect of postoperative treatment was only found in tumors with a high tumor proliferative fraction. Local reactions were similar for the 2 treatment groups, and chronic reactions were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Intratumoral administration of cisplatin is beneficial for treatment of cutaneous tumors in horses. Tumor repopulation during the interval between surgery and intratumoral administration of cisplatin decreases treatment efficacy. These results provide evidence of rapid tumor repopulation following surgical resection without a lag period for tumors with a high proliferation index. When tumor proliferation index is not known, it may be prudent to use the perioperative protocol.

Cobalt 60 irradiation of pituitary gland tumors in three cats with acromegaly.

Acromegaly was diagnosed in 3 cats with insulin-resistant diabetes mellitus (DM) on the basis of history and physical examination findings, which ruled out other causes of insulin-resistant DM, and by documenting high plasma concentrations of growth hormone. Computed tomography revealed a mass in the area of the pituitary gland in each cat. Pituitary gland tumors were irradiated with cobalt 60, and none of the cats developed complications to radiotherapy. Each cat received a total dose of 48 Gy of cobalt 60 during 12 treatments. After completion of radiotherapy, insulin requirements were less for all cats, although in 1 cat, this improvement was transient. Diabetes mellitus resolved in 2 of 3 cats. After treatment, decreases in insulin requirements correlated with decreases in plasma growth hormone concentrations in 2 of 3 cats in which DM resolved. On the basis of these findings, irradiation of pituitary gland tumors appears to be a treatment option for cats with acromegaly.

Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs.

OBJECTIVE: To assess the efficacy and determine prognostic factors of megavoltage irradiation for pituitary macrotumors in dogs with neurologic signs. DESIGN: Prospective clinical trial. ANIMALS: 24 dogs with pituitary macrotumor syndrome; 19 ACTH-secreting and 5 clinically endocrine-inactive tumors. PROCEDURE: Dogs were treated with 48 Gy of radiation during 4 weeks on an alternate-day schedule of 4 Gy/fraction. Three (12.5%) dogs did not complete the planned treatment because of progression of neurologic signs. RESULTS: A significant correlation was found between relative tumor size (i.e., size of tumor relative to calvarium size) and severity of neurologic signs and between relative tumor size and remission of neurologic signs after irradiation. In dogs with pituitary-dependent hyperadrenocorticism, a significant correlation was found between relative tumor size and plasma endogenous ACTH concentrations. Prognostic factors that independently affected duration of remission of neurologic signs were relative tumor size and endocrine activity. The prognostic factor that independently affected overall survival time was severity of neurologic signs. Prognostic factors of duration of eucortisolism were not found. Use of a large field of irradiation was associated with substantial damage to brain tissue. CLINICAL IMPLICATIONS: Because radiation therapy was effective for treatment of tumors of small relative size in dogs, early treatment of pituitary tumors should improve prognosis. Further improvements may be obtained, using protocols in which higher total radiation doses and smaller radiation dose fractions are given. Irradiation was effective for long-term control of functional pituitary macrotumors and resulted in acceptably low complication rates when small fields of radiation were used.

Efficacy of cobalt 60 radiotherapy in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To determine efficacy of cobalt 60 radiotherapy in dogs with pituitary-dependent hyperadrenocorticism (PDH) that have detectable tumors but no neurologic abnormalities. DESIGN: Case series. ANIMALS: 6 dogs with PDH that had a detectable pituitary mass on magnetic resonance images. PROCEDURE: Radiation was delivered in 11 fractions during a 3.5-week period for a total dose of 44 Gy. Clinical signs were evaluated, a urinalysis and ACTH stimulation test were performed, and urine cortisol-to-creatinine ratio and plasma endogenous ACTH concentration were measured before, immediately after, and 1, 3, 6, 9, and 12 months after radiotherapy. Magnetic resonance imaging was repeated 1 year after radiotherapy. RESULTS: Clinical signs of hyperadrenocorticism resolved in 3 dogs but recurred in 2 of the 3. Clinical condition of 2 dogs improved but did not return to normal. One dog did not improve. Results of ACTH stimulation tests and urine cortisol-to-creatinine ratios correlated with clinical signs. Plasma endogenous ACTH concentration transiently decreased in all 6 dogs. One year after radiotherapy, size of tumors was decreased by 25% in 2 dogs; in the other 4 dogs, tumors could no longer be detected. None of the dogs developed neurologic abnormalities. Adverse effects of radiotherapy were mild. CLINICAL IMPLICATIONS: Radiotherapy did not result in adequate control of clinical signs of hyperadrenocorticism in 5 of 6 dogs, but size of pituitary tumors was dramatically reduced. Thus, it may be reasonable to recommend radiotherapy in dogs with PDH that have pituitary tumors for which greatest vertical height is 8 mm or more.

Intralesional and topical chemotherapy and immunotherapy.

Surgery is the mainstay of treatment for equine tumors. Conservative treatment approaches which preserve function and appearance are increasingly used in clinical practice. This article covers the principles and applications of two conservative treatment modalities including local chemotherapy and immunotherapy. The therapeutic benefit of local chemotherapy is based on the direct drug delivery to tumor tissue, i.e., topical and intratumoral administration of cytotoxic agents in slow release formulation. This treatment modality is very effective for cutaneous tumors and does not result in any permanent damage to normal tissue. Immunotherapy produces antitumor effects primarily through the action of natural host defense mechanisms against tumor cells. Although the use of immunotherapy is still under investigation there are many examples of its successful application to treatment of selected equine tumors.

Radiation therapy in the horse.

This article covers the principles and applications of radiation therapy in horses. The goal in treating tumors by irradiation is tumor control with minimum treatment complications. Various treatment techniques are available to achieve this goal. The prognosis depends on many factors such as the extent and location of the tumor, tumor type and tumor cell proliferation. Radiation therapy is a very effective treatment modality for equine tumors but logistical reasons limit its impact in equine oncology.

Comparison of intratumoral administration of cisplatin versus bleomycin for treatment of periocular squamous cell carcinomas in horses.

OBJECTIVE: To compare therapeutic benefits of intratumoral administration of cisplatin and bleomycin for squamous cell carcinoma of the eyelids in horses. ANIMALS: 25 horses with 27 T2-stage periocular squamous cell carcinomas. PROCEDURE: Horses were treated 4 times at 2-week intervals with a slow-release formulation of cisplatin (1 mg/cm3 of tissue) or bleomycin (1 IU/cm3 of tissue). A two-stage design was used to minimize the sample size in each treatment arm. RESULTS: The local control rate at 1 year for lesions treated with cisplatin was 93 +/- 6%, and with bleomycin was 78 +/- 10%. Difference in local control duration between the 2 treatment groups was not significantly different. A high tumor proliferative fraction index value was associated with a higher local (infield) control rate, but also with a higher risk of marginal and regional recurrences. Tumors with a low proliferative fraction index value (< 28%) had 9.5-times higher (P = 0.0411) risk of recurrence than those with a high index value. Local acute reactions were similar in the 2 treatment groups, and chronic reactions were not observed. CONCLUSIONS: Cisplatin and bleomycin were effective anticancer agents for carcinoma of the eyelid in horses. Based on therapeutic benefit and treatment cost, cisplatin was found to be a better choice for intratumoral chemotherapy of eyelid carcinomas. CLINICAL RELEVANCE: Results of this study confirm the value of intratumoral chemotherapy, using cisplatin, for treatment of cutaneous squamous cell carcinomas in horses.