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Background: Administration of streptozotocin (STZ) at a 21-day interval has been described in dogs with stage II and III insulinoma. Myelosuppression was not observed, suggesting the possibility of increasing dose intensity by decreasing the interval between doses., Objective: To describe the tolerability of a biweekly STZ protocol. A secondary objective was to describe the outcome of dogs treated with this protocol., Animals: Nineteen dogs with residual local, metastatic, or recurrent insulinoma., Methods: After surgery for insulinoma, or at the time of recurrence, dogs were treated with a previously described STZ and saline diuresis protocol. Treatments were administered every 14 days. All dogs received antiemetic treatment. Adverse events (AEs) were recorded and graded. Outcome endpoints assessed were progression-free survival (PFS) and survival., Results: None of the dogs experienced neutropenia or thrombocytopenia. Mild to moderate gastrointestinal toxicity was the most common AE. Diabetes mellitus was observed in 8 dogs and, in 6, resulted in euthanasia or death. Two dogs developed nephrotoxicity manifested as Fanconi syndrome in 1 and nephrogenic diabetes insipidus in the other. Six dogs developed increased alanine amino transferase activity. Hypoglycemia at the end of the STZ infusion, resulted in collapse in 1 dog and a generalized seizure in another. The median overall PFS and survival time were 196 and 308 days, respectively., Conclusions and Clinical Importance: Streptozotocin can be safely administered to dogs with insulinoma, but serious AEs are possible. Additional investigation is required to better define the role of STZ in managing dogs with insulinoma., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Purpose: We have noted that inadequate drug delivery to tumor cells is a major cause of failed intravesical therapy for nonmuscle invading bladder cancer, partly due to the dilution of drug concentration by urine production during treatment. To address this problem we developed gelatin nanoparticles of paclitaxel designed to yield constant drug concentrations. The hypothesis that a constant, therapeutic concentration in urine, bladder tissue and tumors can be attained was evaluated in dogs., Materials and Methods: We studied drug release from paclitaxel gelatin nanoparticles in culture medium in vitro. In vivo studies were performed in tumor-free dogs and in pet dogs with naturally occurring transitional cell carcinoma, in which the pharmacokinetics of paclitaxel gelatin nanoparticles were determined in plasma, urine and tumors., Results: Paclitaxel release from paclitaxel gelatin nanoparticles in vitro and in vivo was rate limited by the drug solubility in aqueous medium. This property yielded constant drug concentrations independent of changes in urine volume during the 2-hour treatment. Intravesical paclitaxel gelatin nanoparticles showed low systemic absorption, and favorable bladder tissue/tumor targeting and retention properties with pharmacologically active concentrations retained in tumors for at least 1 week., Conclusions: Constant drug release from paclitaxel gelatin nanoparticles may overcome the problem of drug dilution by newly produced urine and the sustained drug levels in tumors may decrease treatment frequency., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Squamous cell carcinoma (SCC) is a relatively common, malignant neoplasm of dogs and cats that can arise in a variety of locations. The gross appearance of SCC can be variable and nonspecific, so definitive diagnosis requires microscopic examination of the tissue (cytology or histology). Several treatment modalities exist, but surgical excision, if possible, is regarded as the best treatment option. Early diagnosis and treatment of SCC are key because small, early-stage tumors are the most amenable to treatment and carry the best prognosis.

Forty-one dogs with resistant lymphoma were treated with a modified MOPP (mechlorethamine, vincristine, procarbazine and prednisone) protocol (MPP [mechlorethamine, procarbazine and prednisone] administered on a 21-day cycle, shortened from the 28-day MOPP cycle). The overall response rate to MPP was 34% for a median of 56 days (95% confidence interval 30-238). Seventeen percent of dogs had a complete response for a median duration of 238 days, 17% had a partial response for a median of 56 days and 32% had stable disease for a median of 24 days. Histological grade or cell morphology on cytology was associated with response. Minimal toxicity was observed with the MPP protocol, suggesting that further dose intensification or addition of another chemotherapeutic agent would be possible.

A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.

A novel canine lymphoma cell line, OSW, was established from the malignant pleural effusion of a dog with peripheral T-cell lymphoma. The immunoprofile as determined by flow cytometry was as follows: positive for CD45, CD49d, CD18, CD11a; weakly positive for CD11b, CD11c, CD11d; and negative for CD45RA, CD1a, CD1c, CD3, TCRalphabeta, TCRgammadelta, CD4, CD5, CD8a, CD8b, CD90(Thy1), CD21, MHCII, CD14(TUK4), CD34, and MPO. Immunocytochemistry of cytospin preparations was negative for cytoplasmic CD3, CD79a, and MPO, but was positive for CD20. The cell line had an oligoclonal T-cell receptor gamma (TCRgamma) gene rearrangement. Array comparative genomic hybridization (aCGH) and single locus probe (SLP) analysis showed that there were copy number increases of loci on dog chromosome 13 (CFA 13), and copy number decreases were evident for regions of CFA 11, 22, 26, 30 and 32, which include several of the more common chromosomal aberrations reported previously in canine lymphoma. The OSW cell line grows rapidly in vitro and is tumorigenic as a xenograft in SCID/NOD mice. OSW represents one of only a few reported canine lymphoma cell lines and is the most thoroughly characterized. This cell line and xenograft represent significant in vitro and in vivo models, respectively, for comparative and translational lymphoma research.

Background: Various chemotherapy protocols for treating lymphoma in dogs have been published; however, comparison of protocols from different studies is difficult, especially when evaluating survival time and toxicoses., Hypothesis: The choice of COAP (C, cyclophosphamide; O, vincristine; A, cytosine arabinoside; P, prednisone) and a modified University of Wisconsin 19-week (UW-19) induction protocol has no influence on overall survival times in dogs with lymphoma., Animals: One hundred and one dogs with multicentric lymphoma., Methods: Retrospective study (2001-2006). Dogs induced with either an 8-week COP-based protocol (C, cyclophosphamide; O, vincristine; and P, prednisone) with maintenance therapy (COAP group) or a 19-week CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisone) based protocol (UW-19 group) were compared in terms of the duration of first remission, survival time, toxicoses, and cost., Results: There were 71 dogs in the COAP group and 30 dogs in the UW-19 group. Various protocols were used after the first relapse. The median duration of the first remission for the COAP and UW-19 groups were 94 days (range, 6-356 days) and 174 days (28-438 days), respectively (P < .01). The median survival times for dogs in the COAP and UW-19 groups were 309 days (6-620 days) and 275 days (70-1102+ days), respectively (P = .09). Dogs in the COAP group had a hazard ratio of 1.9 (95% CI 1.1-3.4) for death relative to the UW-19 group (P = .03), after controlling for the confounders (World Health Organization clinical stage, age, sex, use of doxorubicin during reinduction). The severity of neutropenia and gastrointestinal toxicoses were significantly higher in the UW-19 group than in the COAP group (P = .01 and P < .01, respectively)., Conclusion and Clinical Importance: Use of a long-term doxorubicin-containing sequential combination chemotherapy protocol is associated with a decreased risk of relapse and death relative to a non-doxorubicin-containing protocol.

Background: Low and nontoxic concentrations (10-50 microM) of suramin, which is a nonspecific inhibitor of multiple growth factors, including fibroblast growth factors, enhances the activities of cytotoxic chemotherapeutic agents, such as doxorubicin and paclitaxel, both in vitro and in vivo. Suramin has not been evaluated as a chemosensitizing agent in dogs with cancer., Hypothesis: Nontoxic suramin can be used safely as a chemosensitizer in dogs., Animals: Sixteen dogs of various breeds with measurable tumors were treated; 1 dog that had undergone amputation for osteosarcoma received adjuvant therapy., Methods: The dogs received 53 courses of treatment with suramin in combination with doxorubicin. The suramin dosage was 6.75 mg/kg IV 3 h before standard doxorubicin administration every 2 weeks. The pharmacokinetics and clinical efficacy were determined., Results: The pharmacokinetics of low-dose suramin followed a 2-compartment model with half-lives of 2 h and 6 days. The distribution volume was a 0.34 +/- 0.12 L/kg, and clearance was 1.86 +/- 0.76 mL/kg/h. During the time interval that doxorubicin was present at therapeutically active concentrations (ie, from the start of infusion to 24 hours), the plasma concentrations were maintained within 20% of the target range (8-60 microM) in 72% of the treatments. The toxicity of the suramin/doxorubicin combination was mild and comparable to the toxicity expected for doxorubicin monotherapy. Objective partial responses were observed in 2 out of 16 evaluable dogs (13%). All 5 dogs that previously received doxorubicin showed improved responses to the suramin/doxorubicin combination., Conclusions and Clinical Importance: A fixed, low-dose suramin regimen yields the desired target plasma concentrations in most dogs, and appears to enhance the activity of doxorubicin without enhancing toxicity.

We conducted a clinical evaluation of gemcitabine in 19 dogs with spontaneously occurring malignancies. The principal objectives of this study were to characterize toxicity and seek preliminary evidence of antitumor activity of gemcitabine administered every 2 weeks (biweekly) as a 30-minute IV infusion. A total of 64 doses, ranging from 300 mg/m2 to 675 mg/m2, were administered during the initial 8-week evaluation period, and an additional 131 doses were administered during the extended evaluation period. The total cumulative dose for the 10 dogs receiving gemcitabine in the extended evaluation period ranged from 1,500 mg/m2 to 24,300 mg/m2. Clinical evidence of toxicity was minimal. Cumulative myelosuppression was not apparent. Unexplained retinal hemorrhages occurred in 1 dog. No complete or partial remissions were observed during the initial evaluation period; however, objective responses were observed in 2 dogs during the extended evaluation period. Gemcitabine is a promising new chemotherapeutic agent that can be used safely in dogs with cancer. Biweekly administration of doses of 675 mg/m2 IV results in minimal and acceptable toxicity.