Initial response to L-asparaginase and prednisolone induction chemotherapy in 107 cases of canine lymphoma

Abstract

Client-owned dogs presented to the Oncology Department of Azabu University Veterinary Teaching Hospital from April 1992 to October 2008 and diagnosed with lymphoma by either diagnostic cytology or histopathology were analyzed retro-spectively（n＝107）. They had not received chemotherapy but may have received prednisolone alone prior to the study. Dogs were assessed within 1 week, and dogs with lymphoblastic leukemia were not included in this study. For initial induction, L-asparaginase and prednisolone were administered, and their initial effects were assessed. The data were assessed at the first visit within 1 week after L-asparaginase induction. Efficacy was assessed based on medical records and the remission rate. Response Evaluation Criteria In Solid Tumors （RECIST） were used to assess the response to treatment ［20］. Complete remission （CR） was defined as disappearance of all target lesions, and partial remission （PR） as a size reduction of ≥ 30％ in the sum of the longest diameters of the lesions. Remission rates were calculated by adding CR and PR. Stable disease（SD）was defined as a reduction of ＜30％ or an increase of ＜20％ in the sum of the longest diameters of the lesions, and progressive disease（PD）was defined as an increase of ≥ 20％ in the sum of the longest diameters of the lesions（the appearance of one or more new lesions was also considered progression）. Except for 2 of the 107 dogs, the dosage of L-asparaginase was 10,000 IU/m 2. For the two dogs, the dosage of L-as-paraginase was 8,000 IU/m 2 , and 5,000 IU/m 2 , respectively. The median dosage of prednisolone was 40 mg/m 2 （range, 10-40 mg/m 2 ）. The recorded data included breed, sex, age, body weight, anatomical site, WHO stage and substage, prior corticosteroid administration, L-asparaginase and prednisolone dosages, initial remission following L-asparaginase induction, improvements in clinical symptoms, and clinical and hematological abnormalities recorded at the first visit after L-asparaginase induction. Improvements in clinical symptoms were assessed by a medical record review of activity, appetite, body weight fluctuation, respiratory symptoms, diarrhea, and ocular lesions. Body weight fluctuations were classified into three cate-gories："Unchanged" was defined for variations within ±＜5％ , "increased" was defined as an increase of ≥ 5％ , and "de-creased" was defined as a decrease of ≥ 5％. Clinical and hematological abnormalities seen at the first visit after L-as-paraginase induction were classified using the veterinary cooperative oncology group common terminology criteria for side effects（VGOG-CTCAE） ［23］. The Mann-Whitney U test was used to compare remission rates in relation to anatomical sites（multicentric and cutane-ous） , stages, substages, and prior corticosteroid administration. The level of significance was set at p＜0.05. Results Twenty-six breeds were represented in this study. The most common breed was Golden Retriever（n＝32, 29.9％） , followed by Shetland Sheepdog（n＝9, 8.4％） , Shih Tzu（n＝8, 7.5％） , Pembroke Welsh Corgi（n＝5, 4.7％）. There were 52 males（15 castrated）and 55 females（31 spayed） , with a median age of 7 years（range, 1-16 years）and a median body weight of 14.5 kg（range, 2.2-67.9 kg）. The anatomical sites were classified as follows（n＝107） ：Multicentric（n＝89, 83.2％） , cutaneous（n＝14, 13.1％） , mediastinal（n＝1, 0.9％） , digestive tract（n＝1, 0.9％） , and duplicate（digestive tract and mediastinal, digestive and multicentric, each n＝1, 1.9％）. Only the multicentric cases（n＝89）were subjected to stage classification：II（n＝3.4％） , III（n＝5, 5.6％） , IV（n＝12, 13.5％） , and V（n＝69, 77.5％） （Table 1）. The classification of substages in the multicentric cases was as follows：Substage-a（n＝33, 37.1％）and substage-b（n＝56, 62.9 ％）. Prednisolone was given prior to L-asparaginase induction chemotherapy in 38 dogs （35.5％） and was not administered in 69 dogs（64.5％）. After administration of L-asparaginase and prednisolone, 104 cases were assessed. There were 29 CR cases（27.9％） , 67 PR cases（64.4％） , 6 SD cases（5.8％） , and 2 PD cases（1.9％）. Three dogs with multicentric lymphoma（2.8％）died within 1 week（Table 2）. The overall remission rate（CR plus PR）was 92.3％. In terms of anatomical sites, the initial remission rate was 96.5％ for multicentric lymphoma（CR：26 cases and PR： 57 cases）in 86 cases, and 78.6％ for cutaneous lymphoma（CR：2 cases and PR：9 cases）in 14 cases；the remission rate was significantly higher for multicentric lymphoma than for cutaneous lymphoma （p＝0.045）. The initial remission rate for