Efficacy of doxorubicin as an induction agent for cats with lymphosarcoma

OBJECTIVE: To determine the efficacy of doxorubicin when used alone in inducing remission in cats with lymphosarcoma. DESIGN: Prospective multi-institutional study of naturally occurring disease. METHODS: Cases were accrued from veterinary institutions in Australia and New Zealand after obtaining consent from informed owners. Cats were treated with doxorubicin every 3 weeks for three treatments. If there was no response to the first dose of doxorubicin or if the cat relapsed during the doxorubicin regimen, the cat was withdrawn from the trial and either euthanased or treated with other agents. Age, breed, gender and anatomic site of the lymphosarcoma (multicentric, alimentary, mediastinal, extranodal) were recorded for each cat. Clinical remission was assessed before each treatment by physical examination, radiography, ultrasonography and computed tomography where appropriate. Complete remission was defined as the disappearance of all clinical signs and clinically detectable tumour. RESULTS: Twenty-one cases were accrued over a 2-year-period but only 19 were available for data analysis. Young Siamese cats were over-represented and all cats with mediastinal tumours were young Siamese. There was a significant difference between the mean ages of cats with mediastinal or multicentric lymphosarcoma (mean +/- SD: 3.5 +/- 3.0 and 4.3 +/- 2.6 years, respectively) and cats with alimentary or extranodal LSA (11.4 +/- 0.9 and 11.0 +/- 0.9 years, respectively). Of 19 cats treated with doxorubicin alone, 6 (32%) had complete remission, 6 (32%) had partial remission and 7 (36%) did not respond. CONCLUSIONS: The results suggest that doxorubicin cannot be recommended as a single agent for treatment of feline lymphosarcoma because of the rather poor remission rate achieved.     

Therapy for Australian cats with lymphosarcoma

OBJECTIVE: To determine the response of Australian cats with lymphosarcoma to chemotherapy and/or surgery in relation to patient and tumour characteristics, haematological and serum biochemical values and retroviral status. DESIGN: Prospective study of 61 client-owned cats with naturally-occurring lymphosarcoma subjected to multi-agent chemotherapy and/or surgery. PROCEDURE: An accepted chemotherapy protocol utilising l-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate and prednisolone was modified and used to treat 60 cats with lymphosarcoma. Clinical findings were recorded before and during therapy. As far as practical, cases were followed to death, euthanasia or apparent cure. Owner satisfaction with the results of chemotherapy was determined using a questionnaire sent after the completion of chemotherapy. RESULTS: One cat, with lymphosarcoma limited to a single mandibular lymph node, was treated using surgery alone and was cured. The other 60 cats were treated using multi-agent chemotherapy, although seven cats with localised intestinal, ocular and subcutaneous lesions had these lesions partially (2 intestinal lesions) or completely (2 eyes, 2 intestinal lesions and a cluster of regional lymph nodes) resected prior to starting chemotherapy. The median survival time for these 60 cats was 116 days. Of the 60 cats, 48 rapidly went into complete remission following the administration of 1-asparaginase, vincristine and prednisolone (complete remission rate 80%) and these cats had a median survival of 187 days. Three cats were censored from further analysis as their long-term survival data were uninterpretable because they died of causes unrelated to lymphosarcoma or were prematurely lost to follow-up. Twenty cats were classed as 'long-term survivors' based on survival time in excess of one year and at least 14 were 'cured' based on the absence of physical evidence of lymphosarcoma 2-years after initiating treatment. In other words, of the 48 cats that reached complete remission, in excess of 29% were 'cured'. Despite detailed analysis, few meaningful prognostic indicators based on patient or tumour characteristics were identified, although long-term survivors were more likely to be less than 4-years (P= 0.04) and to have tumours of the T-cell phenotype (P= 0.06). Excluding the one FeLV ELISA-positive cat with mediastinal LSA, 7 of 9 cats less than 4 years-of-age were long-term survivors (median survival time >1271 days). There was a strong association between achieving complete remission and long-term survival (P = 0.003). On the basis of 27 replies to a questionnaire, owners were generally very satisfied with the response to chemotherapy, irrespective of the survival time of the individual patient. Eighty five percent of owners expressed complete satisfaction with their decision to pursue chemotherapy and 70% believed their cat's health status improved during the first 2-weeks of treatment. Importantly, 78% of owners considered that chemotherapy required a very substantial time commitment on their part. CONCLUSIONS: It was possible to cure approximately one quarter of cats with lymphosarcoma using sequential multi-agent chemotherapy and/or surgery. FeLV-negative cats younger than 4 years (typically with mediastinal lymphosarcoma) had a particularly favourable prognosis. The decision to embark on chemotherapy should be based on the results of induction chemotherapy with l-asparaginase, vincristine and prednisolone, as the response to this was a good predictor of long-term survival. Cats surviving the first 16 weeks of chemotherapy generally enjoyed robust remissions (in excess of 1 year) or were cured of their malignancy.     

Evaluation of the results of a L‐asparaginase‐based continuous chemotherapy protocol versus a short doxorubicin‐based induction chemotherapy protocol in dogs with malignant lymphoma

Summary

The results of an L‐asparaginase‐based continuous chemotherapy protocol (n = 52) versus a short doxorubicin‐based induction chemotherapy protocol (n = 65) were evaluated in 117 dogs with malignant lymphoma. There were no differences between the two groups in patient characteristics or incidence of protocol‐related toxicity. Complete remission was induced in 71.2% of the dogs treated with the Lasparaginase protocol and in 67.7% of the dogs treated with the doxorubicin‐plus protocol. The calculated Kaplan‐Meier one‐ and two‐year survival fractions in the L‐asparaginase group were 48% and 26%, and in the doxorubicin‐plus group 35%, and 22%, respectively. Differences in remission and survival between the two treatment groups were not significant. A multivariate Cox proportional hazards survival analysis revealed that elevated pretreatment plasma creatinine concentration and prior treatment with prednisolone were associated with shorter survival times. An elevated pretreatment plasma creatinine concentration and total leucocyte count were associated with a decrease in the disease‐free period. Differences in efficacy and toxicity between the two protocols were not significant. There is no apparent advantage in using the continuous L‐asparaginase protocol, and the shorter doxorubicin‐plus protocol is less expensive and less time consuming.