Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin

OBJECTIVE: To determine the effectiveness and safety of asparaginase administered s.c. versus i.m. for treatment of multicentric lymphoma in dogs receiving doxorubicin. DESIGN: Prospective study. ANIMALS: 49 dogs with multicentric lymphoma. PROCEDURE: Dogs were treated with doxorubicin every 3 weeks, for a total of 5 treatments, and were given 3 weekly treatments of asparaginase, s.c. or i.m. Using high-performance liquid chromatography, mean plasma asparagine, aspartic acid, glutamine, and glutamic acid concentrations were determined in dogs before and during treatment with asparaginase (10,000 U/m2 of body surface area, once a week for 3 weeks). Asparaginase was administered s.c. in 23 dogs and i.m. in 26 dogs. Variables evaluated included time to response to chemotherapy, remission and survival times, and clinical and serum biochemical indicators of toxicoses. RESULTS: Using the World Health Organization's staging system for lymphoma, 30 dogs were in clinical stage III and 19 were in clinical stage IV. One week after asparaginase treatment, plasma asparagine concentrations were low and plasma aspartic acid, glutamine, and glutamic acid concentrations were high. Differences in plasma amino acid concentrations were not found between s.c. and i.m. groups. For dogs in clinical stage IV, i.m. administration of asparaginase significantly decreased the number of days to complete remission, compared with s.c. administration (8 vs 17 days, respectively). For dogs in clinical stage III, i.m. administration favorably increased the duration of first remission (191 vs 103 days) and survival time (289 vs 209 days). Overall, dogs treated i.m. had a faster response to chemotherapy (9 vs 15 days), a longer remission (191 vs 109 days), and a longer survival time (286 vs 198 days), compared with all dogs treated s.c. Asparaginase toxicoses were not observed regardless of the route of administration. CLINICAL IMPLICATIONS: For dogs with multicentric lymphoma that are receiving doxorubicin, i.m. treatment with asparaginase is more effective than s.c. treatment.     

Prognostic Factors in Dogs with Lymphoma and Associated Hypercalcemia

Lymphoma and hypercalcemia were diagnosed in 37 dogs. Twenty-six of the dogs received chemotherapy. The association between some prognostic factors including clinical stage of disease, illness status, presence of bone marrow involvement, and presence of an anterior mediastinal mass and remission duration and survival time was evaluated. Statistical analysis of the prognostic factors showed that the presence of an anterior mediastinal mass had an adverse effect on remission duration (P less than 0.03). Calcium concentration was not significantly related to any of the prognostic factors evaluated. Dogs that received chemotherapy were more likely to be self-supporting than the dogs that were not treated (P less than 0.005). However, initial illness status was not significantly related to remission duration or survival time in the 26 dogs that were treated. Six dogs (25% of dogs treated) survived longer than 14 months. Five of these dogs were female. Overall mean and median remission times were 10.4 and 6 months, respectively.     

Treatment of Relapsed Canine Lymphoma With Doxorubicin and Dacarbazine

Fifteen dogs with relapsed lymphoma were treated with doxorubicin and dacarbazine (ADIC) to reinduce remission. All the dogs' lymphomas had become resistant to prior therapy with doxorubicin alone. Five of the 15 dogs had a complete response to the first treatment with ADIC, and three had partial responses. Of the eight dogs receiving a second cycle, two had complete responses, and one had a partial response. One dog that received a third ADIC treatment no longer responded. The median survival time from the first ADIC treatment for all dogs was 45 days (range, 18-241 days). The five dogs having complete responses to the first ADIC treatment had a median survival time of 105 days (range, 45-241 days) after this treatment. Toxicity due to ADIC treatment was acceptable and did not exceed that seen when doxorubicin was given as a single agent. The treatment resulted in severe neutropenia in three dogs. One dog died due to neutropenic sepsis. Vomiting, diarrhea, and anorexia occurred, but were tolerable, resulting in hospitalization in only one instance. ADIC is apparently a useful chemotherapeutic combination to reinduce remission in some dogs with relapsed lymphoma.     

Chemotherapy for canine lymphosarcoma.

Twenty dogs with naturally occurring lymphosarcoma were histologically diagnosed, clinically staged, and treated with combinations of drugs, including corticosteroids, alkylating agents, plant alkaloids and antimetabolities. Clinical response was categorized as complete, partial, or unsatisfactory. Of the 20 dogs, 17 responded to the chemotherapy completely or partially, with a mean objective remission duration of 104.8 days. The mean survival time for 19 dogs was 211.5 days, whereas the mean survival time for 16 dogs which responded completely or partially was 233.7 days.     

Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003)

OBJECTIVE: To determine response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol. DESIGN: Retrospective study. ANIMALS: 38 cats with lymphoma. PROCEDURE: Medical records were reviewed, and information on age, sex, breed, FeLV and FIV infection status, anatomic form, clinical stage, and survival time was obtained. Immunophenotyping was not performed. RESULTS: Mean +/- SD age of the cats was 10.9 +/- 4.4 years. Overall median survival time was 210 days (interquartile range, 90 to 657 days), and overall duration of first remission was 156 days (interquartile range, 87 to 316 days). Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first remission or survival time. Eighteen of the 38 (47%) cats had complete remission, 14 (37%) had partial remission, and 6 (16%) had no response. Duration of first remission was significantly longer for cats with complete remission (654 days) than for cats with partial remission (114 days). Median survival time for cats with complete remission (654 days) was significantly longer than median survival time for cats with partial remission (122 days) and for cats with no response (11 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a high percentage of cats with lymphoma will respond to treatment with the University of Wisconsin-Madison chemotherapy protocol. Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first response or survival time, but initial response to treatment was.     

Is Maintenance Chemotherapy Appropriate for the Management of Canine Malignant Lymphoma?

A retrospective study was conducted between two groups of dogs with histopathologically diagnosed multicentric malignant lymphoma to determine if treatment with either short-term or continuous chemotherapy resulted in a significant difference in first-remission length or survival time. One group was treated with single agent, short-term (three cycles) of doxorubicin. Dogs obtaining complete remission while receiving doxorubicin were given no further chemotherapy. The other group received combination agent, long-term chemotherapy consisting of cyclophosphamide, vincristine sulfate, and prednisone (COP). Dogs obtaining complete remission on COP by the end of 6 weeks were given maintenance chemotherapy of cyclophosphamide, prednisone and methotrexate. One hundred and five dogs were treated. Thirty-eight dogs received doxorubicin and 67 received COP. All dogs were evaluated at 6 weeks for response to chemotherapy and followed until death. No significant differences were observed in first-remission length or survival time when comparing dogs treated with either short-term doxorubicin or long-term COP (P greater than 0.05). Sex, weight, age, clinical stage, performance status, histopathologic cell type, and grade were not significant factors for determining the responsiveness to either chemotherapy protocol. However, within either treatment group, significant differences in first-remission length were observed in dogs evaluated histopathologically by the Keil and NCI working formulation and in survival time when evaluated by performance status (P less than 0.05).     

Prognostic factors for tumor remission and survival in dogs after surgery for primary lung tumor: 76 cases (1975-1985)

The association of various prognostic factors with remission and survival after the excision of lung tumors was evaluated in 76 dogs. Overall, the median survival time of treated dogs was 120 days; 72% had tumor that underwent remission (median duration of remission, 120 days). Dogs with tumors that underwent remission had significantly (P = 0.001) increased survival time (median, 330 days vs 28 days for dogs with tumors that did not undergo remission). The finding of normal-sized lymph nodes at the time of therapeutic thoracotomy was significantly (P = 0.001) correlated with increased remission probability (85.4% remission rate vs 43.6% in dogs with large lymph nodes). Use of various diagnostic methods to find normal regional lymph nodes before surgery indicated that such finding was significantly (P less than or equal to 0.01) correlated with increased remission duration (median remission duration, 365 days, vs 60 days for tumors in dogs with large lymph nodes), and the finding of normal lymph nodes at the time of surgery was significantly (P less than or equal to 0.01) correlated with increased survival time (median, 345 days, vs 60 days for dogs with large lymph nodes).     

Retrospective comparison of the efficacy of fluconazole or itraconazole for the treatment of systemic blastomycosis in dogs

Background: Itraconazole is recommended for treatment of blastomycosis in dogs. Some evidence suggests that fluconazole might be less hepatotoxic than itraconazole. Objectives: To compare (1) incidence of clinical remission and death; (2) treatment duration; (3) total drug cost; (4) incidence of relapse; and (5) incidence of increased ALT activities in dogs with blastomycosis treated with fluconazole or itraconazole. Animals: One hundred and forty‐four dogs with systemic blastomycosis treated with itraconazole or fluconazole from 1998 to 2008. Methods: Retrospective case review. Information obtained included signalment, body weight, clinical signs, drug regimen, treatment duration, time to clinical remission, and laboratory results. Results: Neither treatment efficacy between fluconazole (75% remission) and itraconazole (90% remission) nor relapse rate (18% for itraconazole, 22% for fluconazole) was significantly different (P= .13, .75, respectively). Treatment duration was significantly longer for fluconazole (median 183 days) than for itraconazole (138 days; P= .001). Costs for fluconazole (median $1,223) were significantly less than for itraconazole ($3,717; P < .001). Incidence of increased ALT activities was not significantly different between groups (17% [3/18] for fluconazole, 26% [6/23] for itraconazole; P= .71). Conclusions: Fluconazole is associated with survival to clinical remission in 75% of dogs with blastomycosis. Although dogs receiving fluconazole were treated longer, drug costs were one‐third those of itraconazole. Hepatotoxicosis, as estimated by increases in serum ALT activity, can be observed with similar incidence for both drugs.     

Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma

OBJECTIVE: To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin. DESIGN: Nonrandomized controlled clinical trial. ANIMALS: 114 dogs with lymphoma. PROCEDURES: Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or doxorubicin alone (27). RESULTS: 63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage相似文献   

Survival, neurologic response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs

BACKGROUND: Pituitary masses in dogs are not uncommon tumors that can cause endocrine and neurologic signs and, if left untreated, can decrease life expectancy. HYPOTHESIS: Dogs with pituitary masses that received radiation therapy (RT) have more favorable neurologic outcomes and longer survival times compared with untreated dogs. ANIMALS: Nineteen dogs with a pituitary mass identified on CT or MR imaging were irradiated with 48 Gy given in 3 Gy daily-dose fractions. Twenty-seven untreated control dogs had pituitary masses. METHODS: Medical records of dogs with pituitary masses were retrospectively reviewed for clinical signs, mass size, and outcome. RESULTS: Median survival time was not reached in the treated group. Mean survival time in the treated group was 1,405 days (95% confidence interval [CI], 1,053-1,757 days) with 1-, 2-, and 3-year estimated survival of 93, 87, and 55%, respectively. Median survival in the nonirradiated group was 359 days (95% CI, 48-916 days), with a mean of 551 days (95% CI, 271-829 days). The 1-, 2-, and 3-year estimated survival was 45, 32, and 25%, respectively. Dogs that received RT for their pituitary tumors had significantly longer survival times than untreated dogs (P = .0039). Treated dogs with smaller tumors (based on maximal pituitary-to-brain height ratio or area of tumor to area of brain) lived longer than those with larger tumors (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: When compared with untreated dogs, RT increased survival and controlled neurologic signs in dogs with pituitary masses.     

Colorectal adenocarcinoma in dogs: 78 cases (1973-1984)

Colorectal adenocarcinoma was diagnosed in 78 dogs. Clinical signs in all 78 dogs included tenesmus, hematochezia, and dyschezia; most of the dogs had clinical signs less than or equal to 12 weeks before examination. Ultimately, most dogs were euthanatized because of the severity of clinical signs. Proctoscopy and colonoscopy were essential for complete assessment of extent of disease. Tumors were classified by gross appearance and included single, pedunculated masses, 2 or more nodular masses, and annular or intraluminal masses. In dogs in which survival time was compared with location and gross appearance of the tumor, dogs with annular masses had the shortest mean survival time (1.6 months), and dogs with single, pedunculated, polypoid tumors had the longest mean survival time (32 months). The rectum was a more common site than the colon, with 48.2% of the tumors developing in the middle portion of the rectum. Six different modes of surgical treatment were used, depending on the location and type of mass. Dogs that did not have surgical treatment had a mean survival time of 15 months. Mean survival time in the surgically treated dogs varied slightly according to mode of treatment; they survived 7 to 9 months longer than the untreated dogs. Dogs that underwent cryosurgery and local excision had the longest survival times (24 and 22 months, respectively). Statistical analysis disclosed a significantly longer survival time for dogs treated by excision or cryosurgery, as opposed to dogs undergoing biopsy only (P = 0.001). Statistical difference in survival times was not found between dogs that had mass excision and those that had cryosurgery.     

Evaluation of a Multidrug Chemotherapy Protocol (ACOPA II) in Dogs With Lymphoma

A chemotherapeutic protocol using cyclophosphamide, vincristine, prednisone, doxorubicin, and L-asparaginase (ACOPA II) was evaluated in dogs with lymphoma. The response rate for 68 dogs treated with ACOPA II (complete remission [CR] 65%, partial remission [PR] 10%) was lower than that for 41 dogs treated with a related protocol previously evaluated (ACOPA I; CR 76%, PR 12%). Initial treatment with doxorubicin and prednisone did not decrease the prevalence or severity of toxicity during induction. The mortality during induction was 22%. The median duration of CR for dogs treated with ACOPA II was 9 months, with 40% still in remission at 1 year and 21% at 2 years. The rate of CR was lower for dogs with signs of illness at presentation (substage b ) and for dogs weighing less than 15 kg. Age was negatively correlated with survival time and duration of remission. Dogs with immunoblastic lymphoma had a more favorable prognosis than did those with lymphoblastic lymphoma. Survival times were also longer for dogs in substage a at presentation. Seven dogs in which treatment was discontinued while in remission had comparable remission duration to that achieved by dogs receiving long-term maintenance chemotherapy.     

Efficacy of Combination Chemotherapy for Treatment of Gastrointestinal Lymphoma in Dogs

Background: Chemotherapy for multicentric canine lymphoma has favorable results. The gastrointestinal (GI) tract is the most common extranodal site of canine lymphoma, but there have been no prospective studies to determine outcome when dogs with GI lymphoma are treated with chemotherapy.
Hypothesis: Treatment with a multiagent chemotherapy protocol is associated with a poor outcome in dogs with GI lymphoma.
Animals: Eighteen dogs with histologically confirmed GI lymphoma.
Methods: Prospective clinical trial in which dogs with GI lymphoma were treated with a 20-week combination chemotherapy protocol consisting of induction and consolidation phases.
Results: Thirteen dogs had primary GI lymphoma and 5 had multicentric lymphoma with GI involvement. The majority of the lymphomas (63%) were of T-cell origin. Overall remission rate was 56%; 9 dogs achieved a complete remission for a median of 86 days (range, 22–420 days) and 1 dog achieved a partial remission for 26 days. Overall median survival time was 77 days (range, 6–700 days). Dogs that failed to achieve a remission (10 versus 117 days; P = .002) or had diarrhea at initial presentation (70 versus 700 days; P < .001) had shorter survival times.
Conclusion and Clinical Importance: The response and survival of dogs with GI lymphoma treated with multiagent chemotherapy is poor but long-term survival is possible.     

Evaluation of some prognostic factors for advanced multicentric lymphosarcoma in the dog: 147 cases (1978-1981)

A total of 147 dogs treated with a combination of chemotherapy procedure (vincristine, L-asparaginase, cyclophosphamide, and methotrexate) were evaluated for response to therapy and the influence of age, sex, clinical stage, and body weight to duration of response. Complete response was achieved in 113 dogs (77%), partial response in 26 dogs (17.7%), and no response in 8 dogs (5.4%). The median survival time for the dogs with complete and partial responses was 265 days. An analysis of factors associated with prognosis revealed that age, clinical stage, and body weight were not associated with response to therapy, whereas sex was. Females had a significantly prolonged remission and survival time (P = 0.0001).     

Chemotherapeutic responses in dogs with lymphosarcoma and hypercalcemia

Twelve dogs with lymphosarcoma and hypercalcemia were treated over a period of 36 months. Signs and laboratory findings were referable to hypercalcemia and azotemia. All dogs were staged, classified histologically, and given cytoreductive chemotherapy, using 5 drugs (vincristine sulfate, cytosine arabinoside, cyclophosphamide, L-asparaginase and prednisone). For azotemia, symptomatic therapy (0.9% NaCl solution and furosemide) was given. Seven dogs responded completely, with marked reduction of lymphadenopathy and return of serum calcium concentration to normal. Median duration of remission in this group was 48 days (range, 14 to 93), and median survival time was 112 days (range, 85 to 153). Five nonresponding dogs had less than 50% reduction in measurable tumor mass, although serum calcium concentration returned to normal. The median survival time for this group was 34 days (range, 23 to 68). Two of the nonresponders died from sepsis and another from disseminated intravascular coagulation. Response to therapy did not appear to be influenced by age, breed, sex, initial calcium concentration, degree of azotemia, or histologic classification.     

Histologic classification as a prognostic criterion for canine lymphosarcoma

Neoplastic tissues from 72 dogs with lymphosarcoma were histologically classified according to the Rappaport schema to determine if the histologic features of the disease had any clinical or prognostic importance. Of 72 dogs, lymphosarcomas in 7 were classified as nodular (9.7%) and 65 were classified as diffuse (90.3%). The two principal cytologic types were lymphocytic, poorly differentiated, and histiocytic, which composed 39% and 56% of the lymphosarcomas, respectively; whereas lymphocytic, well differentiated, mixed, and undifferentiated composed 6%. Clinically, all of the dogs were stage III or IV, according to the accepted criteria for canine lymphosarcoma. The overall complete remission rate was 64% and was defined as no clinical evidence of disease after 9 weeks of chemotherapy. Median remission among nodular histiocytic, diffuse lymphocytic, poorly differentiated, and diffuse histiocytic (DH) groups of dogs was 42 days, 29 days, and 42 days (range, 0 to 1,095), respectively. Median survival for the same groups was 235 days, 190 days, and 173 days (range, 1 to 1,261), respectively. A logarithmic analysis of variance revealed no significant differences among nodular histiocytic, diffuse lymphocytic, poorly differentiated, and DH groups relative to days remission, as well as to days survival. It was observed that those dogs with neoplasms classified as DH had longer remission durations. It would appear that for any one animal, histologic classification according to the Rappaport schema cannot be used as a prognostic criterion in predicting therapeutic response, remission, or survival.     

Evaluation of survival times after limb amputation, with and without subsequent administration of cisplatin, for treatment of appendicular osteosarcoma in dogs: 30 cases (1979-1990).

Appendicular osteosarcoma was diagnosed in 30 dogs. Fifteen dogs were treated by limb amputation alone, and 15 dogs were treated by limb amputation followed by 2 doses of cisplatin given IV approximately 2 and 7 weeks after limb removal. Mean survival time after limb amputation alone +/- SD was 190 +/- 138 days (median, 168 days); 7 dogs survived longer than 6 months, and 3 dogs survived more than 1 year. Fourteen of 15 dogs treated by amputation and administration of cisplatin survived a mean of 315 +/- 158 days (median, 290 days) after amputation, and 1 dog was still alive at 1,095 days; 13 dogs survived longer than 6 months and 5 dogs survived more than 1 year. Survival time was significantly (P less than 0.05) greater in dogs given cisplatin.     

Radiotherapy of malignant nasal tumors in 67 dogs

The nasal cavity of 67 dogs with malignant nasal neoplasia was treated with radiation. Preirradiation surgical cytoreduction of the tumor was done in 41 dogs. Fifty dogs were irradiated by use of 10 fractions over 22 days, and 17 dogs were given a similar total dose in 5 fractions over 35 days. The range of survival times (0.5 to 42 months), median survival time (8.5 months), and 1- and 2-year survival rates (38% and 30%, respectively) were better than those expected for other methods of treatment. Serious complications were few (4%). Survival times for dogs were determined on the basis of histologic tumor type and on the basis of megavoltage (cobalt or linear accelerator) vs softer deep radiation (cesium or orthovoltage) treatment, with or without cytoreductive surgery. Survival times of 10 dogs given softer radiation without surgery were shorter than those of 14 dogs that were given softer radiation and had cytoreductive surgery. Survival times of dogs that were given softer radiation and had surgery were similar to those of dogs that were given megavoltage radiation only. Cytoreductive surgery did not improve survival times for dogs that were given megavoltage radiation. Median survival time for 38 dogs with adenocarcinoma was 12 months, compared with 6 months for 14 dogs with squamous cell or undifferentiated carcinoma. Median survival time for 16 dogs with a variety of sarcomas was 11.2 months. Survival times of dogs with adenocarcinoma or sarcoma were significantly better (P less than 0.02 or 0.03) than for dogs with squamous cell or undifferentiated carcinoma. Necropsies were performed on 27 of 58 dogs that died or were euthanatized.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carmustine, vincristine, and prednisone in the treatment of canine lymphosarcoma

A chemotherapeutic protocol using carmustine in combination with vincristine and prednisone was tested in dogs with multicentric malignant lymphosarcoma. Of seven dogs treated, six (85.7%) achieved complete remission. A partial response occurred in one dog. Median survival time was 224 days (mean 386 days), and median duration of remission was 183 days (mean 323 days). Marked neutropenia was observed following carmustine administration. There were no significant alterations in platelets and red blood cell counts during treatment, and no abnormalities attributable to the chemotherapy were found in serum biochemical profiles. Results of this study showed that carmustine is an effective alternative option in the treatment of canine lymphosarcoma.     

Radiotherapy of brain tumors in dogs

Brain tumors in 4 dogs were treated with external beam, megavoltage radiation. X-ray computed tomography was used to localize and characterize brain tumors and to assess treatment response. Total radiation doses were 3,000 or 3,600 rad, given in 5 or 6 fractions over 14 to 19 days. Complete tumor regression, as determined from computed tomography scans, improvement in clinical signs, and reduction in medication, were documented in all irradiated dogs. The median survival time for irradiated dogs was 322 days, which was significantly (P less than 0.05) longer than the median survival time of 56 days in 8 dogs with brain tumors treated symptomatically. The one-year survival rate for the irradiated dogs, after correcting for deaths from intercurrent disease, was 100%. It was concluded that canine brain tumors may be treated effectively by use of megavoltage radiation.