Immunohistochemical characterization of feline mast cell tumors.

Expression of histamine, serotonin, and KIT was evaluated in 61 archived feline mast cell tumors (MCTs) from the skin (n = 29), spleen (n = 17), and gastrointestinal (GI) tract (n = 15) using immunohistochemistry. Twenty-eight percent of cutaneous MCTs, 18% of splenic MCTs, and 53% of GI MCTs displayed histamine immunoreactivity. Serotonin immunoreactivity was detected in 3 GI and 1 cutaneous MCT. Sixty-nine percent of cutaneous MCTs, 35% of splenic MCTs, and 33% of GI MCTs were positive for KIT. Expression of these biogenic amines and KIT was less common than expected. Results of this study suggest heterogeneity in feline MCTs based on anatomic location. Further studies are needed to explain the significance of these differences.

Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsy specimens in veterinary surgical pathology.

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.

Phase II, open-label trial of single-agent CCNU in dogs with previously untreated histiocytic sarcoma.

BACKGROUND: Histiocytic sarcoma (HS) is an aggressive neoplasm in dogs, and in most instances, the disease is localized, but not amenable to surgical removal, or is disseminated. Affected patients usually die within 6 months. There have been no prospective studies to determine efficacy of single-agent chemotherapy in dogs with HS. HYPOTHESIS: Single-agent CCNU [1-(2-chloroethyl)3-cyclohexyl-1-nitrosourea; lomustine] has antitumor activity against HS in dogs. ANIMALS: Twenty-one dogs with histologically confirmed, nonresectable localized or disseminated HS. METHODS: Prospective, open-label phase II clinical trial in which dogs with previously untreated HS were uniformly treated with CCNU as a single oral dosage of 90 mg/m2 every 4 weeks. The primary outcome measure was reduction in tumor size. RESULTS: Fourteen dogs with disseminated HS and 7 with localized HS were enrolled between 1999 and 2008. Overall response rate was 29% (95% confidence interval [CI], 14­50%) for a median of 96 days (95% CI, 55­137 days). Three dogs (1 disseminated, 2 localized) had complete responses lasting for 54­269 days and 3 dogs (2 disseminated, 1 localized) had partial responses lasting for 78­112 days. CONCLUSIONS AND CLINICAL IMPORTANCE: CCNU, when used as a single agent, has activity against HS in dogs. Evaluation of CCNU postoperatively for dogs with resectable localized HS and as part of combination therapy for tumors that are nonresectable or disseminated should be considered.

Phase I dose escalating study of oral cyclophosphamide in tumour-bearing cats.

Cyclophosphamide is an alkylating agent used to treat cats with lymphoma, carcinomas and sarcomas. However, no clear consensus exists regarding the maximum tolerated dose (MTD) of oral cyclophosphamide in cats. Toxicities are rarely reported at published oral dosages of cyclophosphamide (200-300 mg/m2). The primary aim of this prospective study was to determine the MTD of oral cyclophosphamide in tumour-bearing cats via a modified phase I trial. A secondary aim was to define any toxicity. Forty-six client-owned tumour-bearing cats were enrolled. The cyclophosphamide dosage was escalated by approximately 10% (300, 330, 360, 400, 440, 460 and 480 mg/m2) in cohorts of at least six cats. The MTD of oral cyclophosphamide in this study was 460 mg/m2 with an inter-treatment interval of two to three weeks. Haematology is recommended 7 and 14 days after first cyclophosphamide treatment, and immediately before each subsequent dosage of cyclophosphamide or any potentially myelosuppressive chemotherapy agent. The dose-limiting toxicity was neutropenia with nadir at 7-21 days. This higher dosage was considered safe in combination with prednisolone and L-asparaginase. However, the higher dose of oral cyclophosphamide has not been evaluated in combination with other chemotherapy agents and thus should not be administered with these agents.

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.

Phase I dose escalation of single-agent vinblastine in dogs.

BACKGROUND: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. HYPOTHESIS: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. ANIMALS: Twenty-three dogs with lymphoma or cutaneous mast cell tumors. METHODS: Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2-3 weeks. RESULTS: VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.

Combination of CCNU and DTIC chemotherapy for treatment of resistant lymphoma in dogs.

BACKGROUND: Pleotropic-glycoprotein (P-gp)-mediated resistance is the usual cause of relapse in dogs with lymphoma. 1-(2-chloroethyl)3-cyclohexyl-1-nitrosurea (CCNU) and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) are alkylating agents that are not affected by P-gp and lack cross-resistance to each other. A combination protocol offers the advantage of improved summation dose and synergistic activity. HYPOTHESIS: A combination of CCNU and DTIC that is well tolerated can be used to treat dogs with lymphoma that developed resistance or failed to respond to previously administered chemotherapy. ANIMALS: Fifty-seven dogs with lymphoma that were resistant to treatment with standard chemotherapy (L-CHOP; L-asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisone). METHODS: Prospective phase I and II trials were performed. CCNU was given PO immediately before a 5-h IV infusion of DTIC. Concurrent antiemetics and prophylactic antibiotics were used. Treatments were administered every 4 weeks. RESULTS: Based on the results of 8 dogs in the phase I study, CCNU at 40 mg/m(2) PO combined with DTIC at 600 mg/m(2) IV was used to treat 57 dogs with resistant lymphoma. Thirteen (23%) dogs had a complete response (CR) for a median of 83 days and 7 (12%) had a partial response for a median of 25 days. The median L-CHOP CR duration of the dogs that did not respond to CCNU-DTIC was significantly longer than that of the dogs that did achieve remission with CCNU-DTIC (225 days versus 92 days, P= .02). The principal toxic event was neutropenia; the median neutrophil count 7 days after treatment was 1,275 cells/microL. Increases in alanine transaminase activity, possibly associated with hepatotoxicity, were detected in 7 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of CCNU and DTIC can be an effective option to rescue dogs with resistant lymphoma.

Efficacy of vinblastine for treatment of canine mast cell tumors.

BACKGROUND: The optimal dosage and clinical efficacy of vinblastine (VBL) for treatment of mast cell tumors (MCTs) in dogs has not been established. HYPOTHESIS: Single-agent VBL has antitumor activity against MCTs in dogs. ANIMALS: Fifty-one dogs with nonresectable grade II or III cutaneous MCTs. METHODS: Prospective, open clinical trial. Dogs were systematically allocated (by hospital record number) to receive IV treatment with VBL at a dosage of 2.0 mg/m2 (weekly for 4 treatments then biweekly for 4 treatments; VBL 2.0) or treatment with VBL at a dosage of 3.5 mg/m2 (biweekly for 5 treatments; VBL 3.5). The primary outcome measure was reduction in tumor size. RESULTS: Twenty-five dogs were allocated to the VBL 2.0 group and 26 were allocated to the VBL 3.5 group. In the VBL 2.0 group, 3 (12%) had a partial response (PR) for a median of 77 days (range, 48-229 days). Overall response rate in the VBL 3.5 group was 27%. One dog (4%) had a complete response for 63 days and 6 dogs (23%) had a PR for a median of 28 days (range, 28-78 days). Toxicoses were uncommon in the VBL 2.0 group. Twelve (46%) dogs in the VBL 3.5 group had < 500 neutrophils/microL 7 days after treatment; 2 dogs with neutropenia developed concurrent fevers. CONCLUSIONS AND CLINICAL IMPORTANCE: VBL, when used as a single-agent, has activity against MCTs in dogs although the response rate is lower than those reported for VBL-containing combination protocols. Further, findings suggest VBL at a dosage of 3.5 mg/m2 should be considered for use in future phase II/III trials.

Prophylactic trimethoprim-sulfadiazine during chemotherapy in dogs with lymphoma and osteosarcoma: a double-blind, placebo-controlled study.

BACKGROUND: The administration of chemotherapy is associated with risk for morbidity. Management of chemotherapy-related morbidity in veterinary oncology has been primarily supportive. HYPOTHESIS: The purpose of this study was to evaluate the effect of prophylactic antimicrobial use on chemotherapy-associated morbidity in dogs with lymphoma or osteosarcoma. ANIMALS: Dogs presenting with histologically confirmed osteosarcoma or lymphoma were eligible. METHODS: Patients were randomized to receive placebo or trimethoprim-sulfadiazine for 14 days after their first doxorubicin chemotherapy. Both owner and clinician were blinded with respect to treatment. Patient assessment included CBC, physical examination and performance, and toxicosis grading on days 7 and 14. Investigated outcomes were hospitalization, suspicion of infection, gastrointestinal toxicity, neutropenia, nonhematologic toxicity, and quality of life. RESULTS: Seventy-three dogs were enrolled; 34 had osteosarcoma, and 39 had lymphoma. Dogs receiving trimethoprim-sulfadiazine (n = 36) had a significantly reduced hospitalization rate (P = .03), nonhematologic toxicity (P = 0.039), grade 2-4 nonhematologic toxicity (P < .0001), grade 2-4 gastrointestinal toxicity (P = .007). and altered performance (P = .015). By group, dogs with osteosarcoma (n = 34) that received the antimicrobial experienced fewer occurrences of nonhematologic toxicity (P = .02) and less severe nonhematologic toxicity (P = .038). Dogs with lymphoma (n = 39) had significant reductions in the occurrence of hospitalization (P = .035), severity of nonhematologic toxicity (P = .036), and alterations of performance (P = .015). CONCLUSIONS: The use of prophylactic trimethoprim-sulfadiazine has benefit in reducing morbidity in dogs with osteosarcoma or lymphoma during the first 14 days after treatment with doxorubicin.

Orthovoltage radiation and weekly low dose of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs.

The efficacy and toxicity of orthovoltage radiation therapy and concurrent low doses of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs was investigated retrospectively. The 39 dogs had 40 soft-tissue sarcomas and received 51 Gy orthovoltage radiation in 17 daily 3 Gy fractions; they also received 10 mg/m(2) doxorubicin once a week administered intravenously one hour before the dose of radiation. The median follow-up time was 910 days. The tumours recurred locally in seven of the dogs, in five of them within the radiation field; the median time to their recurrence was 213 days (range 63 to 555 days). Six of the dogs developed a distant metastasis after a median time of 276 days (range eight to 826 days). The one-year and two- to four-year tumour control rates were 84 per cent and 81 per cent, respectively, and the one-, two- and three- to four-year survival rates were 85 per cent, 79 per cent and 72 per cent, respectively. Tumours with a mitotic rate of more than 9 per 10 high-power fields were significantly more likely to recur, and the dogs with such tumours survived for significantly shorter periods.

Phase I and pharmacokinetic evaluation of the combination of orally administered docetaxel and cyclosporin A in tumor-bearing cats.

Intravenously administered docetaxel (DT) is problematic in cats because of the requirement for premedication to ameliorate acute vehicle-induced hypersensitivity reactions. Previously we have revealed that therapeutic plasma concentrations of DT can be achieved in normal and tumor-bearing dogs when DT is administered PO in combination with oral cyclosporin A (CSA). The purpose of this study was to identify the maximally tolerated dosage and characterize the pharmacokinetic disposition of oral DT combined with CSA in cats with tumors. Eighteen tumor-bearing cats were enrolled in this phase I dose escalation and pharmacokinetic study. DT was administered by gavage with CSA (5 mg/kg) twice over a 3-week period. The starting dose of DT was 1.0 mg/kg. Based on the clinical toxicity profile, with gastrointestinal adverse effects and hematologic toxicity the maximal tolerated dose of oral DT was 1.75 mg/kg in combination with 5 mg/kg CSA. Additional studies are necessary to determine the efficacy of DT/CSA in cats with epithelial tumors.

A prospective evaluation of the impact of second-opinion histopathology on diagnostic testing, cost and treatment in dogs and cats with cancer.

Second-opinion histopathology is a common practice in human medicine to avoid unnecessary procedures, costs and to optimize therapy. Histopathology review has been recommended in veterinary oncology as well. In this prospective evaluation of 52 tumours over a 1-year period, there was diagnostic agreement between first and second opinions in 52% of cases. Twenty-nine percent of cases had partial diagnostic disagreement, most often a change in grade, tumour subtype or margin status. Nineteen percent had complete diagnostic disagreement, including a change in cell of origin or a change from benign to malignant. Minor disagreements, which would not affect treatment or prognosis, were present in 21% of cases. Major disagreements, which would affect either treatment or prognosis, were present in 37% of cases. Costs of ideal staging and treatment recommendations were considerably different between first and second opinions.

Biological behaviour of canine mandibular osteosarcoma. A retrospective study of 50 cases (1999-2007).

The purpose of this retrospective study was to describe the biological behaviour of canine mandibular osteosarcoma (OSA) and to examine factors for their impact on metastasis-free interval (MFI) and survival time (ST). Records from dogs treated with mandibulectomy for OSA (1999-2007) were reviewed. Archived tumour samples were evaluated for mitotic index (MI) and tumour grade. Fifty dogs were included, 21 received chemotherapy. Twenty-nine dogs (58%) developed metastatic disease. The median MFI was 627 days, and median ST was 525 days. In univariate analysis MI > 40 was prognostic for decreased MFI and ST. Grade also influenced MFI and ST, with 5/21 (24%) dogs with grade II/III tumours metastasis-free at one year versus 16/22 (72%) dogs with grade I tumours (P = 0.002); and 5/21 (24%) dogs with grade II/III tumours alive versus 17/22 (77%) dogs with grade I tumours (P = 0.001). In multivariate analysis, histological grade and adjuvant chemotherapy were prognostic for MFI and ST.

Retrospective study of orthovoltage radiation therapy for nasal tumors in 42 dogs.

Megavoltage radiation therapy currently is the standard of care for dogs with nasal tumors. Some studies report that surgery and adjunctive orthovoltage radiation therapy result in longer control of these tumors than does megavoltage radiation therapy alone. This study reports less effective control of nasal tumors in dogs treated with surgery and orthovoltage radiation than previously observed, supporting the superiority of megavoltage radiation therapy for these tumors. In addition, this study suggests 2 new prognostic indicators for dogs with nasal tumors and describes toxicity associated with surgery and orthovoltage therapy. Forty-two dogs with nasal tumors were treated with surgical cytoreduction and 48 Gy orthovoltage radiation therapy administered in twelve 4-Gy fractions. Median survival was 7.4 months. One- and 2-year survival rates were 37% and 17%, respectively. Dogs with facial deformity had shorter survival than those without deformity (P = .005). Dogs with resolution of clinical signs after treatment had longer survival than those with chronic nasal signs (P = .0001). Acute radiation toxicity was moderate to severe for skin and eye and negligible for oral mucosa. Toxicity healed within 1 month after radiation therapy. Late toxicity was mild, but 70% of evaluable dogs experienced persistent ocular signs. Only 39% of dogs achieved a disease-free period.

Phase I evaluation of CCNU (lomustine) in tumor-bearing cats.

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.

Evaluation of ifosfamide for treatment of various canine neoplasms.

lfosfamide (3-[2-chloroethyl]-2[(2 chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) is an alkylating agent with a broad spectrum of antitumor activity. The efficacy and toxicity of ifosfamide were evaluated in 72 dogs with spontaneously occurring tumors. Forty dogs (56%) had lymphoma, 31 (43%) had sarcomas, and 1 had a metastatic carcinoma. Five dogs received ifosfamide at dosages <350 mg/m2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m2 (n = 18) and 375 mg/m2 body surface area IV (n = 49). Saline diuresis and the thiol compound mesna were used to prevent urothelial toxicity. Fifty-two dogs had measurable tumors and could be evaluated for response. Complete responses were seen in 1 dog with metastatic leiomyosarcoma of the urinary bladder and in 1 dog with metastatic cutaneous hemangiosarcoma. One dog with lymphoma had a partial response for 112 days. Six dogs with splenic hemangiosarcoma received ifosfamide postsplenectomy and their median survival time was 147 days. The acute dose limiting toxicity was neutropenia 7 days after administration of ifosfamide. The median and mean neutrophil counts 7 days after ifosfamide at 350 mg/m2 were 2,035 cells/microL and 4,773 cells/microL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m2 were 2,500 cells/microL and 3,594 cells/microL, respectively (n = 37). No dog developed clinical or microscopic evidence of hemorrhagic cystitis. Ifosfamide appears safe to use in tumor-bearing dogs, and the evaluation of combination chemotherapy protocols that include ifosfamide should be considered.

Treatment of canine mast cell tumors with CCNU (lomustine).

The efficacy and toxicity of CCNU (1-[2-chloroethyl]3-cyclohexyl-1-nitrosourea) were evaluated in 23 dogs with measurable mast cell tumors (MCT). Twenty-two dogs had cutaneous MCT and 1 dog had an intranasal MCT Nineteen (83%) dogs had biopsy of their original mass performed and 4 (17%) had aspiration cytology of masses. Of the 19 tumors histologically graded, 1 (5%) neoplasm was classified as grade I, 10 (53%) were grade II, and the remaining 8 (42%) were grade III. Dogs were treated with CCNU at a dosage of 90 mg/m2 body surface area every 3 weeks. Response could be evaluated in 19 dogs. Eight of the 19 dogs (42%) had a measurable response to CCNU. One dog had a durable complete response for 440 days. Seven dogs (37%) had a partial response for a median and mean duration of 77 days and 109 days, respectively (range, 21-254 days). Treatment with CCNU resulted in stable disease in 6 dogs (32%) for a median and mean duration of 78 days and 122 days, respectively (range, 42-347 days). The acute dose-limiting toxicity was neutropenia 7 days after administration of CCNU. The median and mean neutrophil counts 7 days after CCNU were 1,452 cells/microL and 1,683 cells/microL, respectively (n = 17). Other toxicoses were uncommon. CCNU should be considered an active agent in the treatment of MCT in dogs.

Prognostic value of argyrophilic nucleolar organizer region (AgNOR) staining in feline intestinal lymphoma.

Limited information is available on prognostic factors for cats with lymphoma. The quantity of argyrophilic nucleolar organizer region (AgNOR) proteins can be used as a measurement of cellular proliferative activity. To determine if AgNORs were of prognostic value for feline intestinal lymphoma, the silver staining technique was performed on paraffin-embedded sections of 31 cases. Mean number of AgNORs per nucleus ranged from 1.02 to 4.32. Twenty-four (78%) cats had small AgNORs and 7 (22%) had large AgNORs. All cats were treated identically with a combination chemotherapy protocol. Response to chemotherapy was 87%. Median remission duration and survival times were 120 days and 201 days, respectively. No significant correlation was found between mean number of AgNORs per nucleus or AgNOR size and remission rate, remission duration, or survival time. This study indicates that AgNOR staining is not a useful prognostic factor for cats with intestinal lymphoma.

Use of a vascular access system for administration of chemotherapeutic agents to a ferret with lymphoma.

Two months after initiation of chemotherapy, a totally implantable vascular access system was used for the continuing administration of chemotherapeutic agents to a ferret with multicentric lymphoma. The subcutaneously located injection port minimized the need for restraint and facilitated repeated IV administration of drugs. Treatment with a combination of L-asparaginase, vincristine sulfate, doxorubicin, cyclophosphamide, methotrexate, chlorambucil, and prednisone failed to induce complete remission. Survival time (interval from histologic diagnosis to euthanasia) was 10 months. The vascular access system remained patent and did not cause infection in the surrounding subcutaneous tissues during the 5-month period that it was in position.