Objective—To determine clinical activity and toxic effects of ifosfamide when used to treat cats with vaccine-associated sarcoma (VAS).
Animals—27 cats with a nonresectable, recurrent, or metastatic VAS.
Procedure—Each cat received ifosfamide (900 mg/m2 of body surface area) as an IV infusion during a 30-minute period. Diuresis by infusion of saline (0.9% NaCl) solution and administration of mesna were used to prevent urothelial toxicosis. Treatments were administered every 3 weeks, and tumor response was assessed after the second treatment. All ifos-famide-associated toxic effects were graded in accordance with predetermined criteria.
Results—61 treatments were administered to 27 cats (median, 2 treatments/cat; range, 1 to 4 treat-ments/cat). After ifosfamide treatment, 1 cat had a complete response and 10 had partial responses for an overall response rate of 11 of 27 (41%; 95% confidence interval [CI], 25% to 59%). Responses lasted from 21 to 133 days (median, 70 days; 95% CI, 60 to 113 days). The acute dose-limiting toxicosis was neutropenia, which was detected 5 to 28 days (median, 7 days) after treatment. Median nadir neutrophil count was 1,600 cells/μL (range, 200 to 5,382 cells/μL). Nine (33%) cats had adverse gastrointestinal effects (primarily salivation during the ifosfamide infusion and inappetence after treatment). Two cats were euthanatized because of severe nephrotoxicosis, and 1 cat developed pulmonary edema during diuresis.
Conclusions and Clinical Relevance—Ifosfamide has antitumor activity against VAS in cats and is tolerated well by most cats. Ifosfamide should be evaluated as an adjuvant treatment for cats with VAS.
Objective—To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of ifosfamide in tumor-bearing cats.
Animals—38 cats with resected, recurrent, or metastatic sarcomas.
Procedure—The starting dosage of ifosfamide was 400 mg/m2 of body surface area, IV, and dosages were increased by 50 to 100 mg/m2 in cohorts of 3 cats. To protect against urotoxicosis, mesna was administered at a dosage equal to 20% of the calculated ifosfamide dosage. Diuresis with saline (0.9% NaCl) solution before and after administration of ifosfamide was used to minimize nephrotoxicosis. Samples for pharmacokinetic analysis were obtained after the MTD was reached.
Results—38 cats were entered into this phase I study and were administered a single dose of ifosfamide at various dosages. The MTD was 1,000 mg/m2, and neutropenia was the DLT. Seven of 8 episodes of neutropenia were on day 7 after treatment, and 1 cat developed severe neutropenia on day 5. Adverse effects on the gastrointestinal tract were generally mild and self-limiting, the most common of which was nausea during ifosfamide infusion. One cat had signs consistent with a drug-induced hypersensitivity reaction. There were no episodes of hemorrhagic cystitis or nephrotoxicosis. Correlations between pharmacokinetic variables and ifosfamide-associated toxicoses were not found. Preliminary evidence of antitumor activity was observed in 6 of 27 cats with measurable tumors.
Conclusions and Clinical Relevance—The dosage of ifosfamide recommended to treat tumor-bearing cats is 900 mg/m2 every 3 weeks. This dosage should be used in phase II clinical trials.
Objective—To determine toxic effects of streptozocin
given in combination with a diuresis protocol in dogs
and establish whether streptozocin is efficacious in
treatment of pancreatic islet cell tumors in dogs.
Procedure—Medical records were reviewed to
obtain information regarding signalment, tumor stage
and staging tests performed, number of streptozocin
treatments, adverse effects, results of biochemical
and hematologic monitoring during streptozocin treatment,
tumor dimensions, duration of normoglycemia,
and date of death, when applicable. Dogs were compared
with a historical control group of 15 dogs treated
surgically and medically.
Results—58 treatments were administered to the 17
dogs. Only 1 dog developed azotemia. Serum alanine
aminotransferase activity increased in some dogs but
decreased when treatment was discontinued.
Hematologic toxicoses were rare. Vomiting during
administration was uncommon but occasionally
severe. Two dogs developed diabetes mellitus after
receiving 5 doses. Median duration of normoglycemia
for 14 dogs with stage-II or -III insulinoma treated with
streptozocin was 163 days (95% confidence interval,
16 to 309 days), which was not significantly different
from that for the control dogs (90 days; 95% confidence
interval, 0 to 426 days). Two dogs had rapid resolution
of paraneoplastic peripheral neuropathy, and 2
others had measurable reductions in tumor size.
Conclusions and Clinical Relevance—Results
suggest that streptozocin can be administered safely
to dogs at a dosage of 500 mg/m2, IV, every 3
weeks when combined with a protocol for induction
of diuresis and may be efficacious in the treatment
of dogs with metastatic pancreatic islet cell tumors.
(J Am Vet Med Assoc 2002;221:811–818)
Objective—To determine clinical activity and toxic effects of lomustine when used to treat cats with mast cell tumors (MCTs).
Design—Retrospective case series.
Animals—38 cats with measurable, histologically or cytologically confirmed MCTs treated with lomustine at a dosage ≥ 50 mg/m2.
Procedures—Medical records were reviewed to determine response to treatment and evidence of drug toxicoses. The Kaplan-Meier method was used to estimate remission duration.
Results—26 cats had cutaneous MCTs, 7 had MCTs of the mesenteric lymph nodes, 2 had gastrointestinal tract MCTs, 2 had hepatic MCTs, and 1 had MCTs involving multiple organs. Targeted lomustine dosage was 50 mg/m2 in 22 cats and 60 mg/m2 in 16 cats. Median administered dosage of lomustine was 56 mg/m2 (range, 48 to 65 mg/m2), and median number of doses administered was 2 (range, 1 to 12). Seven cats had a complete response and 12 had a partial response, for an overall response rate of 50%. Median response duration was 168 days (range, 25 to 727 days). The most common toxicoses were neutropenia and thrombocytopenia.
Conclusions and Clinical Relevance—Results suggested that lomustine had activity against MCTs in cats and was well tolerated. Further, findings suggested that treatment with lomustine should be considered for cats with MCTs for which local treatment is not an option.
Objective—To determine outcome of dogs with presumed primary hepatic lymphoma treated with various multiagent, doxorubicin-based chemotherapeutic protocols and identify factors associated with prognosis.
Design—Retrospective case series.
Animals—18 dogs with presumed primary hepatic lymphoma.
Procedures—Medical records were reviewed for information on signalment, treatment, and outcome.
Results—8 dogs had a complete remission (CR), with a median remission duration of 120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia, hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia were less likely to achieve a CR. Overall median survival time (MST) was 63 days (range, 2 to 402 days). In a multivariate analysis, response to treatment and serum albumin concentration were associated with MST. Dogs that did not achieve a CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283 days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time treatment was initiated had a significantly shorter MST than did dogs with serum albumin concentration within reference limits (10 vs 128 days, respectively). There was also a positive correlation between serum albumin concentration and survival time (r = 0.74).
Conclusions and Clinical Relevance—Results suggested that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor prognosis, with a low response rate. Dogs that responded to treatment had a better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.
Objective—To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment.
Design—Retrospective case series.
Animals—139 dogs with histologically confirmed nasal carcinomas.
Procedures—Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived ≥ 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model.
Results—Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days).
Conclusions and Clinical Relevance—The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.