Dacarbazine as Single-Agent Therapy for Relapsed Lymphoma in Dogs

Background: Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5-(3,3-Dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma.
Hypothesis: Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy.
Animals: Forty client-owned dogs with relapsed lymphoma.
Methods: Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800–1,000 mg/m² every 2–3 weeks as a 4–5-hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed.
Results: The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7–14 days after the treatment. Treatments were delayed because of thrombocytopenia.
Conclusions: DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma.     

Evaluation of Prognostic Factors and Sequential Combination Chemotherapy With Doxorubicin for Canine Lymphoma

Fifty-five dogs with lymphoma were treated using a doxorubicin-based sequential combination chemotherapy protocol. Complete response, partial response, and no response were seen in 46, 4, and 5 dogs, respectively. The overall median remission duration and survival times were 36 and 51 weeks, respectively. Age, sex, weight, World Health Organization stage, World Health Organization substage (i.e., a = not ill, b = ill), serum calcium concentration, blood urea nitrogen concentration, breed, and protocol alteration secondary to toxicity were evaluated for prognostic significance. Univariate analysis of prognostic factors identified sex, World Health Organization substage, and serum calcium as statistically significant ( P ≤ .05) variables for both survival and remission duration. Upon multivariate analysis, only substage ( P = .036) was a significant prognostic factor for remission duration, whereas, both substage ( P = .006) and sex ( P = .005) were significant prognostic factors for survival. (Journal of Veterinary Internal Medicine 1993; 7:289–295. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Chemotherapy of Canine Hemangiosarcoma With Doxorubicin and Cyclophosphamide

Sixteen dogs with a histologic diagnosis of hemangiosarcoma were treated with surgery and doxorubicin/ cyclophosphamide. The patients' characteristics, ie, age, size, and breed, were similar to those of previous studies. Historic controls for surgery alone were used to evaluate efficacy of the chemotherapy. The results show a trend of improved survival in dogs with localized disease (Stage I) receiving combination therapy. The median survival was 250 days, with a mean of 403 days. The survival times for dogs with stage I, II, and III disease was also improved with combination therapy, when compared to historical controls treated with surgery alone. The overall median survival was 202 days with a mean of 285 days. Toxicities included mild to moderate neutropenia (9 of 16) and clinical signs, such as lethargy, anorexia, vomiting, diarrhea, and fever (13 of 16). Three dogs had severe neutropenia requiring hospitalization and supportive care. One dog died from sepsis and related complications. Chemotherapy with doxorubicin and cyclophosphamide appears to improve survival with acceptable morbidity in patients with early stage disease. (Journal of Veterinary Internal Medicine 1993; 7:370–376. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Combination Chemotherapy with Continuous l-Asparaginase, Lomustine, and Prednisone for Relapsed Canine Lymphoma

Background: The combination of lomustine, l -asparaginase, and prednisone (LAP) is an effective rescue treatment for canine lymphoma (LSA). In a previous study, we reported that remission was typically lost around the time l -asparaginase was discontinued.
Hypothesis: Use of l -asparaginase with each lomustine treatment will be well tolerated and efficacious as a rescue therapy for canine LSA.
Animals: Forty-eight client-owned dogs with cytologically confirmed multicentric LSA whose disease had relapsed after a cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy protocol were included.
Methods: Lomustine was administered orally at 3-week intervals, concurrently with subcutaneous or intramuscular l -asparaginase for a total of 5 doses or until disease progression. Prednisone was administered at a tapering dose for the duration of the protocol.
Results: The overall response rate (ORR) for dogs treated with this protocol was 77%, with 65% achieving a complete response (CR). The median time to progression (TTP) was 70 days. Based on loose comparison, these findings are not significantly different from our previously reported historical control. The actual CCNU dosage administered did not affect response rate or remission duration.
Conclusions/Clinical Importance: These findings support previous data concluding that the LAP protocol is a viable rescue treatment option for dogs with LSA. However, results from this study suggest that continued use of l -asparaginase with each lomustine treatment does not significantly increase remission duration and toxicity appears greater.     

Half-Body Radiotherapy in the Treatment of Canine Lymphoma

In a Phase I-II study, half-body radiotherapy was used to treat 14 dogs with multicentric lymphoma. Using this technique, a radiation dose of 7 Gray (Gy) was delivered to one half of the body in a single exposure. The other half of the body was treated approximately 28 days later. Of 14 treated dogs, 11 (79%) had a measurable decrease in tumor size. Five dogs achieved a complete or partial remission with a mean duration of 102 and 54 days, respectively. In predicting response to therapy, poor prognostic factors included large tumor burdens, advanced disease stage, and chemotherapy-resistant tumors. Side effects of treatment were divided chronologically into acute (radiation sickness, tumor lysis), subacute (bone marrow suppression), and chronic (radiation pneumonitis, lymphoma-cell leukemia) syndromes. Complications were more severe in tumor-bearing dogs when compared with healthy control animals. Dogs with small tumor burdens and minimal internal disease had fewer complications compared with those with more advanced disease.     

母犬二次膀胱尿道结石症的诊治

犬尿路结石在徐州地区发病较高,并且复发率较高,给家庭养犬业造成了极大的影响.犬尿路结石主要发生于老龄公犬,笔者最近在临床上接诊一例复杂的母犬膀胱尿道结石病例,尤其尿道结石较大,处理起来非常困难,最后采用尿道口切开术,将结石顺利取出.犬尿路结石的手术疗法国内一般采用膀胱切开术和尿道切开术,采用尿道口切开术尚属首例.     

母犬二次膀胱尿道结石症的诊治

犬尿路结石在徐州地区发病较高,并且复发率较高,给家庭养犬业造成了极大的影响。犬尿路结石主要发生于老龄公犬,笔者最近在临床上接诊一例复杂的母犬膀胱尿道结石病例,尤其尿道结石较大,处理起来非常困难,最后采用尿道口切开术,将结石顺利取出。犬尿路结石的手术疗法国内一般采用膀胱切开术和尿道切开术,采用尿道口切开术尚属首例。     

A Comparison of Doxorubicin and COP for Maintenance of Remission in Cats With Lymphoma

Thirty-eight cats with lymphoma were treated with vincristine, cyclophosphamide, and prednisone (COP). They were randomized at entry to receive maintenance chemotherapy consisting of either single-agent doxorubicin or continued COP therapy, starting on week 4 of treatment and continuing for 6 months or until relapse. Eighteen cats achieved complete clinical remission after COP induction chemotherapy. The median remission duration for 11 cats continuing to receive COP was 83 days, which was significantly shorter than for 7 cats that received doxorubicin (281 days). Thus, doxorubicin should be considered a well-tolerated and efficacious agent for the maintenance of remission in cats with lymphoma.     

Alpha-fetoprotein in Canine Multicentric Lymphoma

The concentrations of AFP were evaluated in the sera from groups of healthy dogs and of dogs with multicentric lymphoma, before and while receiving chemotherapy. The concentration of AFP was highest in the affected dogs, especially during the fifth stage of lymphoma. Chemotherapy caused a decrease in AFP serum concentration, during both the induction and the maintenance phases of treatment, when compared to the same animals before therapy. Determination of the concentration of AFP in the serum may be an additional indicator in the evaluation of the stage of lymphoma, and of value in assessing the extent of neoplastic infiltration of the liver.     

Sequential Low-Dose Rate Half-Body Irradiation and Chemotherapy for the Treatment of Canine Multicentric Lymphoma

Background: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels.
Hypothesis: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs.
Animals: Thirty-eight client-owned animals diagnosed with multicentric lymphoma.
Methods: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy.
Results: The median 1st remission was 410 days (95% confidence interval [CI] 241–803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334–1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%.
Conclusions and Clinical Relevance: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.     

Alterations in Carbohydrate Metabolism in Canine Lymphoma

Following an overnight fast, blood samples were obtained from 14 dogs with previously untreated lymphoma before and 5, 15, 30, 45, 60, and 90 minutes following an intravenous challenge with 500 mg/kg dextrose. Samples were assayed for glucose, lactate, and insulin concentrations and compared statistically with ten control dogs of similar weight and age undergoing an identical dextrose challenge. Dogs with lymphoma had similar glucose tolerance curves when compared with controls. Lactate concentrations were significantly higher (P less than 0.001) at baseline and all time periods of the glucose tolerance test in dogs with lymphoma when compared with controls. Rise in lactate concentrations over baseline levels in the first 30 minutes of the glucose tolerance test were significantly higher in dogs with lymphoma (P = 0.011). Insulin concentrations were significantly higher (P less than 0.001) at baseline and at the 5-, 45-, 60-, and 90-minute time periods of the glucose tolerance test in dogs with lymphoma. Rise in insulin concentrations over baseline in the first 5 minutes of the glucose tolerance test were also significantly greater in dogs with lymphoma (P = 0.021). These results indicate carbohydrate metabolism is altered in dogs with lymphoma. Many of these alterations parallel those observed in human patients suffering from cancer cachexia making canine lymphoma a potential model for further study of the pathogenesis and therapy of cancer cachexia.     

Response of Canine Mast Cell Tumors to Treatment With Oral Prednisone

Twenty-five dogs with naturally occurring mast cell tumors were treated with daily oral prednisone (1 mg/kg) for 28 days. Five dogs (20%) had reduction in tumor volume and were considered responders. Four of these underwent partial remission and one underwent complete remission. Survival times for the five responders were 3, 5, 6, 7.5, and greater than 28 months, respectively. We therefore conclude that prednisone is effective in some canine mast cell tumors. Further studies are indicated to determine the most effective dose of prednisone, the appropriate duration of treatment, and the efficacy in more benign mast cell tumors, and in combination with other forms of therapy.     

Surgery and Doxorubicin in Dogs With Hemangiosarcoma

Forty-six dogs with histologically confirmed hemangiosarcoma of various locations other than skin were used in a prospective study to determine the efficacy of adjuvant doxorubicin (30 mg/m² IV q 3 weeks for 5 treatments) 10 to 14 days after the tumor was partially or completely excised. Analysis of the data included information on variables that were hypothesized to influence response to therapy, disease-free interval (DFI), or survival time (ST). Other information collected included age, gender, breed, weight, prior therapy, type of surgery, location of the primary tumor, presence of metastases, number of doses of doxorubicin, response to doxorubicin therapy (complete or partial response!, and the following histological criteria: overall differentiation, nuclear pleomorphism, percent necrosis, mitotic score, total histological score, and grade. Surgery outcome (complete versus incomplete surgical excision) markedly influenced survival times (P < .001). Twenty percent of the dogs rendered free of disease were alive at 1 year, whereas none of the dogs that had residual tumor after surgery were alive at 1 year. Most of the histological criteria (nuclear pleomorphism, mitotic score, grade, overall differentiation) had marked (P < .05), or close to marked, independent associations with ST for dogs that had complete tumor removal. Results from analysis of DFI were generally similar to those of ST in dogs with complete excision of the tumor. Twenty-seven of the 46 dogs (58.7%) had all clinical evidence of tumor successfully removed. Logistic regression analysis of surgical outcome (ability to remove all visible tumor) suggested that age of the subject was the only factor markedly influencing surgical outcome (P= .017). As age increased, the probability of success increased. Those dogs that had previous treatment for their hemangiosarcoma tended (P= .08) to have a shorter DFI and ST. Therefore, complete removal of all evidence of tumor followed by 5 doses of doxorubicin may be an effective treatment for dogs with hemangiosarcoma. Dogs that had all tumor successfully removed had a mean and median ST of 267 and 172 days, respectively. Dogs with incomplete tumor removal had a mean and median ST of 172 and 60 days, respectively. Similarly, prognostic variables such as the ability to completely excise all evidence of tumor, histological criteria, and age of the patient are potentially important prognostic variables for predicting outcome.     

Phase I Evaluation of Doxorubicin and Whole-body Hyperthermia in Dogs with Lymphoma

Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

犬瘟热病毒初期感染的治疗

犬瘟热,俗称狗瘟,是一种主要危害幼犬的严重犬类疾病.其病原体是犬瘟热病毒.寒性地带生活的犬种易患该病,死亡率较高. 犬瘟热潜伏期为3～9天.犬瘟热开始的症状是体温会升高,持续1～3天,然后消退,类似感冒痊愈症状.但几天后体温会再次升高,持续时间不定,呈双相热型;可见有流泪、眼结膜发红,眼分泌物由液状变成黏脓性鼻液等症状.病初干咳,后转为湿咳、呼吸困难;呕吐、腹泻、肠套迭、最终严重脱水并衰弱死亡.     

Evaluation of Single-Agent Mitoxantrone as Chemotherapy for Relapsing Canine Lymphoma

Many chemotherapeutic regimens will induce remission in dogs with lymphoma, but almost all dogs suffer relapse. Mitoxantrone was selected for evaluation as single-agent chemotherapy for relapsing canine lymphoma based on its use in humans undergoing salvage chemotherapy for non-Hodgkin's lymphoma and its tumoricidal effect against canine lymphoma. Dogs entered into study had multicentric lymphoma, and all had been treated solely with a standard combination chemotherapy protocol. At 1st relapse, all dogs were again staged and underwent lymph node biopsy. Mitoxantrone was administered IV at 6 mg/m² every 21 days. Dogs were evaluated for lymphadenopathy before each dose of mitoxantrone. Fifteen dogs were entered into study. The average age (±SEM) of the dogs studied was 7.7 ± 0.91 years, and most dogs were large (mean ± SEM weight, 24.44 ± 2.15 kg). Twelve dogs (80%) had B-cell lymphoma, and 3 had T-cell lymphoma. Dogs were staged IV (n = 12) or V (n = 3). The median duration of chemotherapy before entry into the study was 98 days. Overall median duration of response after mitoxantrone chemotherapy was 21 days. Complete responses were attained in 7 of 15 dogs (47%) with a median response duration of 84 days. Nine of 15 (60%) dogs attained a complete remission with additional chemotherapy after failing mitoxantrone chemotherapy. Mild toxicities were observed after mitoxantrone administration. No adverse reactions were observed during mitoxantrone infusions. The results of this study demonstrate that mitoxantrone, as a single agent, has limited value for dogs with lymphoma at 1st relapse after conventional multidrug chemotherapy.