Evaluation of a high-dose chemotherapy protocol with no maintenance therapy for dogs with lymphoma

The purpose of this study was to evaluate the efficacy and toxicity of an intensified dose protocol with no maintenance phase for the treatment of canine lymphoma. Forty-nine dogs all weighing more than 15 kg were entered. Dogs were staged and treated with a modified version of the University of Wisconsin (UW)-Madison protocol for lymphoma. Modifications included increased dosages of cyclophosphamide (250 mg/m² compared to 200 mg/m²) and doxorubicin (37.5 mg/m² compared to 30 mg/m²), with no crossover to chlorambucil or methotrexate. After 25 weeks on protocol (17 treatments), therapy was discontinued and dogs were monitored for relapse on a monthly basis. Disease-free interval (DFI) and overall survival were compared to 55 historical controls treated with the UW-Madison protocol. The 2 groups were comparable with respect to age, sex, breed, stage, presence of hypercalcemia, and CD3 status; a trend toward more substage b dogs was present in the high-dose group ( P = .076). When comparing response rate, DFI, death due to disease, and death due to treatment-related toxicity, more dogs were dead due to toxicity ( P < .001; odds ratio = 8.8) in the high-dose group. Overall survival between the high-dose and control groups did not differ significantly ( P = .55) at 270 and 318 days, respectively. The intensified dose protocol is an option for owners who are willing to risk higher toxicity for a shorter protocol with no statistical difference in survival from the UW-Madison protocol.     

Effects of L-asparaginase on plasma amino acid profiles and tumor burden in cats with lymphoma

BACKGROUND: L-Asparaginase (Elspar(a)), is an Escherichia coli-derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L-asparaginase on plasma amino acid concentrations is unknown. HYPOTHESES: L-Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats. ANIMALS: Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L-asparaginase for initial LSA treatment. METHODS: Plasma collected at 0, 2, and 7 days after L-asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response. Results: Eight cats had T-cell LSA, 4 cats had B-cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L-asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged. CONCLUSIONS AND CLINICAL IMPORTANCE: L-asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L-asparaginase in this study was 30%.