Jennifer L. Baez

Efficacy and Toxicity of a Dose‐Intensified Doxorubicin Protocol in Canine Hemangiosarcoma

The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-intensified doxorubicin protocol in canine hemangiosarcoma (HSA). Canine HSA is a highly malignant tumor, and most affected dogs die within 6 months of diagnosis. Doxorubicin is the most, and possibly the only, effective chemotherapeutic drug for this malignancy, but it provides only moderate improvement in survival. On the basis of previous studies reporting similar survival in dogs treated with doxorubicin as a single agent and doxorubicin-based combination chemotherapy and the concept of summation dose intensity, a dose-intensified single-agent doxorubicin protocol was initiated. Twenty dogs with HSA were recruited to participate in this study. Workup and staging were performed according to standard practice. Chemotherapy was initiated within 3 weeks of surgery. Doxorubicin was scheduled to be administered at 30 mg/m2 i.v. every 2 weeks for a total of 5 treatments. The dogs were monitored for toxicity and signs of recurrence during and at regular intervals after chemotherapy. The protocol was tolerated well. No dogs were hospitalized because of adverse effects or developed clinical signs consistent with doxorubicin-induced cardiomyopathy. There was a significant difference in survival in dogs with stage I and I1 HSA compared with dogs with stage III HSA. with median survival times of 257, 210, and 107 days, respectively. These results are slightly better than the historical control with respect to toxicity and efficacy but are not statistically different from what is achieved with standard treatments. There was no association between dose intensity and outcome.

A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients.

The objectives of this study were to prospectively identify and characterize weight loss and changes in body condition in feline cancer patients and to investigate the prognostic significance of these findings. Fifty-seven cats with neoplasia were evaluated. Body condition was assessed with a nine-point scoring system (BCS) and multiple sites were assessed for muscle and fat mass using four-point scoring systems. Feline cancer patients had a mean BCS of 4.4±2.1 kg (1=cachectic, 5=optimal, 9=obese). Fat mass was reduced in both sites assessed in 60% of the patients. Muscle mass was reduced at all three sites assessed in 91% of the patients. Feline cancer patients having a BCS <5 had a median survival time (MST) of 3.3 months compared to that of 16.7 months for cats with a BCS of ≥5 (P=0.008).

Lomustine for treatment of mast cell tumors in cats: 38 cases (1999–2005)

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 > or = 50 mg/m(2). 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/m(2) in 22 cats and 60 mg/m(2) in 16 cats. Median administered dosage of lomustine was 56 mg/m(2) (range, 48 to 65 mg/m(2)), 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.

Feline Visceral Hemangiosarcoma

BACKGROUND Feline visceral hemangiosarcoma (HSA) is an uncommon tumor, and the clinical progression and outcome are rarely reported. HYPOTHESIS The prognosis of feline visceral HSA is poor because of severe clinical signs, anemia, and a high rate of metastasis. ANIMALS The medical records of 26 client-owned cats with visceral HSA were reviewed. METHODS Multi-institutional retrospective study. RESULTS The most common historical findings and clinical signs included lethargy, anorexia, respiratory difficulty, collapse, and vocalizing. Eighty-two percent of cats were anemic, and aspartate transaminase was increased in 53% of the study population. Metastatic lung disease was noted in 33% of affected cats. In 75% of the cats, abdominal ultrasonography identified a specific location of HSA. However, ultrasound identification of all multifocal lesions was successful only in 3/9 cats (33%). Tumor location was identified in the following organs: liver (35%), small intestine (31%), large intestine (31%), abdominal lymph node (31%), mesentery (27%), spleen (23%), lung (19%), omentum (12%), brain (8%), pancreas (8%), and diaphragm (8%). Multifocal HSA was noted in 77% of cats. Three cats received adjuvant chemotherapy (doxorubicin). Seventy-one percent of euthanized cats were euthanized within 1 day of diagnosis. The median survival time of the remaining cats (n = 6) was 77 days (range, 23-296 days). CONCLUSION AND CLINICAL IMPORTANCE Feline visceral HSA is most often multifocal at the time of diagnosis. The prognosis appears poor, and the number of cats receiving chemotherapy is low.

Clinical and Pharmacokinetic Characteristics of Intracavitary Administration of Pegylated Liposomal Encapsulated Doxorubicin in Dogs with Splenic Hemangiosarcoma

BACKGROUND Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. HYPOTHESIS Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. ANIMALS Fourteen dogs with splenic HSA. METHODS A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. RESULTS All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. CONCLUSIONS AND CLINICAL IMPORTANCE IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.