Clinical evaluation of gemcitabine in dogs with spontaneously occurring malignancies

We conducted a clinical evaluation of gemcitabine in 19 dogs with spontaneously occurring malignancies. The principal objectives of this study were to characterize toxicity and seek preliminary evidence of antitumor activity of gemcitabine administered every 2 weeks (biweekly) as a 30-minute IV infusion. A total of 64 doses, ranging from 300 mg/m2 to 675 mg/m2, were administered during the initial 8-week evaluation period, and an additional 131 doses were administered during the extended evaluation period. The total cumulative dose for the 10 dogs receiving gemcitabine in the extended evaluation period ranged from 1,500 mg/m2 to 24,300 mg/m2. Clinical evidence of toxicity was minimal. Cumulative myelosuppression was not apparent. Unexplained retinal hemorrhages occurred in 1 dog. No complete or partial remissions were observed during the initial evaluation period; however, objective responses were observed in 2 dogs during the extended evaluation period. Gemcitabine is a promising new chemotherapeutic agent that can be used safely in dogs with cancer. Biweekly administration of doses of 675 mg/m2 IV results in minimal and acceptable toxicity.     

Single agent chemotherapy with doxorubicin for feline lymphoma: a retrospective study of 19 cases (1994-1997)

Medical records of 21 cats with confirmed lymphoma treated with single-agent doxorubicin were reviewed. Nineteen cats met the inclusion criteria for this retrospective study. Doxorubicin was given at a dosage of 25 mg/m2 (n = 8) or 1 mg/kg (n = 11) IV, every 3 weeks for a total of 5 treatments. Four of 16 tested cats were positive for feline leukemia virus (FeLV) and all 16 cats tested negative for feline immunodeficiency virus. Eight of the 19 cats (42%) responded to doxorubicin for a median duration of 64 days (range, 35-575 days). Five cats (26%) achieved a complete response (CR) to doxorubicin for a median duration of 92 days (range, 54-575 days). Partial response was observed in 3 cats. Institution was the only significant prognostic indicator for response, with cats treated at Colorado State University being more likely to achieve CR than cats treated at Tufts University. Cats that achieved CR to doxorubicin and FeLV-negative cats had significantly longer survival times. Loss of appetite was the most common toxicity, observed in 9 cats (47%), and was severe in 5 cats (26%). Other toxicoses were less frequent and included vomiting, diarrhea, and myelosuppression. Doxorubicin was not very effective at inducing and maintaining remission in the cats in this study. Therefore, if doxorubicin is used for the treatment of feline lymphoma, it should be combined with other effective chemotherapeutic drugs in a combination protocol.     

Dexamethasone, melphalan, actinomycin D, cytosine arabinoside (DMAC) protocol for dogs with relapsed lymphoma

BACKGROUND: In general, treatment of relapsed lymphoma is associated with a lower probability of response and shorter duration of remission. The purpose of this study was to evaluate the efficacy of the combination chemotherapy protocol DMAC (dexamethasone, melphalan, actinomycin D, and cytosine arabinoside) for reinduction of remission in dogs with relapsed lymphoma. HYPOTHESIS: That DMAC would be an effective reinduction protocol for dogs with relapsed lymphoma. ANIMALS: Fifty-four dogs. RESULTS: Seventy-two percent of the dogs achieved remission (44% complete remission [CR] and 28% partial remission [PR]), 11% had stable disease (SD), and 17% had progressive disease (PD). The median remission duration was 61 days (range, 2-467+ days). The median remission durations for dogs with CR, PR, and SD were 112, 44, and 27 days, respectively. Factors that affected the response rate were previous treatment with doxorubicin and an inability to achieve remission with the previous protocol. Thrombocytopenia occurred in 56% of the dogs (grade 1 in 3 dogs, grade 2 in 6 dogs, grade 3 in 7 dogs, and grade 4 in 7 dogs) and neutropenia in 17% of the dogs (grade 2 in 1 dog, grade 3 in 2 dogs, and grade 4 in 4 dogs). Gastrointestinal toxicosis occurred in 22% of the dogs (grades 1 in 5 dogs, grade 2 in 3 dogs, and grade 3 in 1 dog). CONCLUSIONS AND CLINICAL IMPORTANCE: The DMAC protocol is an effective rescue protocol for dogs with relapsed multicentric lymphoma. Although thrombocytopenia is a common manifestation of toxicity, in general, the protocol is well tolerated.     

Evaluation of satraplatin in dogs with spontaneously occurring malignant tumors

Background: Satraplatin is the 1st orally bioavailable platinum anticancer drug. Objective: Our objectives were to evaluate efficacy in vitro against a canine cancer cell line, to determine the maximally tolerated dose (MTD) of satraplatin in tumor‐bearing dogs, to identify the dose‐limiting and other toxicities in dogs, and to record pharmacokinetics (PK). Animals: Dogs with macro‐ or microscopic malignant neoplasia. Methods: D17 canine osteosarcoma cells first were evaluated in a clonogenic survival assay. Then, dogs with a diagnosis of malignant neoplasia were prospectively entered in standard 3 + 3 cohorts. Additional patients were entered at the MTD to assess efficacy. Total and free platinum (by ultrafiltrate) concentrations were determined with inductively coupled plasma mass spectroscopy. Results: Satraplatin inhibited clonogenic survival in vitro at clinically relevant and achievable concentrations. Twenty‐three dogs were treated, 14 with PK evaluation. The MTD was 35 mg/m²/d for 5 days, repeated every 3–4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included T_max 1.8 (± 0.7) hours, C_max 72 (± 26) ng/mL, area under concentration (AUC)_{0–24 h} 316 (± 63) h × ng/mL, and MRT 7 (± 1.3) hours. Higher AUC after the 5th versus the 1st dose suggested drug accumulation. Interestingly, platelets consistently reached nadir sooner than did neutrophils (day 14 versus 19). Myelosuppression was dose‐limiting and gastrointestinal toxicity was mild. Conclusions and Clinical Importance: Satraplatin was well tolerated in tumor‐bearing dogs, thus warranting further investigation in a phase II trial.     

Evaluation of a high-dose chemotherapy protocol with no maintenance therapy for dogs with lymphoma

The purpose of this study was to evaluate the efficacy and toxicity of an intensified dose protocol with no maintenance phase for the treatment of canine lymphoma. Forty-nine dogs all weighing more than 15 kg were entered. Dogs were staged and treated with a modified version of the University of Wisconsin (UW)-Madison protocol for lymphoma. Modifications included increased dosages of cyclophosphamide (250 mg/m² compared to 200 mg/m²) and doxorubicin (37.5 mg/m² compared to 30 mg/m²), with no crossover to chlorambucil or methotrexate. After 25 weeks on protocol (17 treatments), therapy was discontinued and dogs were monitored for relapse on a monthly basis. Disease-free interval (DFI) and overall survival were compared to 55 historical controls treated with the UW-Madison protocol. The 2 groups were comparable with respect to age, sex, breed, stage, presence of hypercalcemia, and CD3 status; a trend toward more substage b dogs was present in the high-dose group ( P = .076). When comparing response rate, DFI, death due to disease, and death due to treatment-related toxicity, more dogs were dead due to toxicity ( P < .001; odds ratio = 8.8) in the high-dose group. Overall survival between the high-dose and control groups did not differ significantly ( P = .55) at 270 and 318 days, respectively. The intensified dose protocol is an option for owners who are willing to risk higher toxicity for a shorter protocol with no statistical difference in survival from the UW-Madison protocol.     

Clinical evaluation of methoximorpholino-doxorubicin (FCE 23762) in dogs with spontaneous malignancies

We conducted a clinical evaluation of FCE 23762, a methoxymorpholino analog of doxorubicin, in 48 dogs with metastatic, nonresectable, or chemotherapy-resistant spontaneous malignancies at an initial dosage of 50-60 microg/kg IV every 3 weeks. Clinical evidence of toxicity was minimal; 6 dogs developed grades I, II, and III hematologic toxicities after the 1st treatment, and 1 dog developed grade II gastrointestinal toxicity. One dog became pancytopenic 4 months after discontinuation of FCE 23762. No other adverse effects were noted. Partial or complete remissions were observed in 32% of the dogs. Responses were observed both in previously untreated dogs and in those that had received prior chemotherapy, including doxorubicin. FCE 23762 is a promising new antineoplastic agent that can be used safely in dogs with cancer; doses higher than those used in this study may be used eventually in practice.     

Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma

The purpose of this study was to compare a maintenance-free chemotherapy protocol based on CHOP (H from hydroxydaunorubicin = doxorubicin, O from Oncovin = vincristine) to a similar protocol with a maintenance phase for the treatment of canine lymphoma. Fifty-three dogs with multicentric lymphoma were treated with a 6-month modified version of the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25). Disease-free interval (DFI) and survival were compared to a historical control group of 55 dogs treated with a similar protocol with a prolonged maintenance phase. Remission rate for the study dogs was 94.2% (complete remission = 92.3%, partial remission = 1.9%). DFI and survival between the 2 groups did not differ significantly, with median DFI and survival of the study dogs equal to 282 and 397 days compared to 220 and 303 days for the control dogs (P = .2835 and .3365, respectively). Univariate analysis identified substage b (P = .0087), German Shepherd breed (P = .0199), and body weight > 18 kg (P = .0016) as significant for worse survival. Longer survival was associated with thrombocytopenia (P = .0436). Multivariate analysis revealed that substage (P = .0388) and weight (P = .0125) retained significance for DFI, whereas substage (P = .0093), thrombocytopenia (P = .0150), and weight (P = 0 .0050) retained significance for survival. Overall, the protocol was well tolerated by the dogs, with 41.5% (22/53) requiring a treatment delay or dose modification, but only 9.4% (5/53) needing hospitalization. The 6-month chemotherapy protocol based on CHOP with no maintenance phase provides similar DFI and survival times when compared to a similar protocol with a prolonged maintenance phase.     

MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000)

The purpose of this retrospective study was to evaluate the efficacy and toxicity of the MOPP chemotherapy protocol (mechlorethamine, vincristine, procarbazine, and prednisone) as a rescue regimen in dogs with lymphoma. One hundred seventeen dogs that had resistance to previously administered chemotherapy were evaluated. Before treatment with MOPP, all dogs received a median of 6 chemotherapy drugs for a median duration of 213 days. Thirty-one percent (36 of 117) had a complete response (CR) to MOPP for a median of 63 days, and 34% (40 of 117) had a partial response (PR) for a median of 47 days. Sixteen percent (19 of 117) had stable disease (SD) for a median of 33 days. Predictors for response to MOPP were not identified. Gastrointestinal (GI) toxicity occurred in 28% (33 of 117) of the dogs, and 13% (15 dogs) required hospitalization. Five dogs developed septicemia, and 2 died as a result. MOPP was an effective treatment for dogs with resistant lymphoma and was well tolerated by the majority of affected dogs.     

Neutropenia associated with vincristine and L-asparaginase induction chemotherapy for canine lymphoma

Vincristine (VCR) and L-asparaginase (L-ASP) are commonly used to treat canine lymphoma. As single agents, these drugs are not myelosuppressive. However, in combination, VCR and L-ASP cause severe neutropenia in some dogs. It has been recommended that L-ASP be administered 12-24 hours after VCR to minimize toxicity. The purpose of this retrospective study was to determine the prevalence of neutropenia after VCR/L-ASP induction therapy for canine lymphoma and to evaluate risk factors for myelosuppression, especially the interval between VCR and L-ASP administration. Medical records of 147 dogs were reviewed. L-ASP was given 0 (n = 50), 6 (n = 23), 18 (n = 20), or 24 (n = 54) hours after VCR. Forty percent of the dogs were neutropenic 7 days after VCR/L-ASP, and 18% had neutrophil counts of <1,000 cells/microL. The median neutrophil count was 3,712 cells/microL (range 0-30,968 cells/microL). No correlation was found between administration interval and day 7 neutrophil count (P = .84) or development of gastrointestinal signs, including vomiting (P = .80), diarrhea (P = .52), and decreased appetite (P = .30). No significant predictors of neutropenia were identified. Higher clinical stage and substage b were associated with decreased appetite after treatment (P = .04 and .01, respectively). Sixteen percent of the dogs were hospitalized. This study demonstrates that VCR/L-ASP induction for canine lymphoma may result in neutropenia but that separation of VCR and L-ASP administration may not be necessary to avoid toxicity.     

Single-agent gemcitabine chemotherapy in dogs with hepatocellular carcinomas

The goal of this study was to determine the efficacy and tolerability of gemcitabine in dogs diagnosed with hepatocellular carcinoma (HCC). Eighteen dogs were examined retrospectively (4 massive HCC, 10 nodular HCC and 4 diffuse HCC). All dogs received gemcitabine at 350-400 mg m(-2) weekly for 5 weeks. Toxicity was graded using VCOG-CTCAE guidelines and response was monitored with serial abdominal ultrasounds. Fifteen dogs completed all five cycles. Toxicity was minimal and consisted of grade I/II vomiting, anorexia and diarrhoea and two episodes of grade III neutropenia. Median survival time for all dogs was 983 days. Median progression free interval was 971 days. Based on the results of this study, surgery remains the best treatment for HCC, despite incomplete resection. There was no improvement in the survival of those diagnosed with nonresectable HCC treated with gemcitabine chemotherapy.     

Combination chemotherapy with L-asparaginase, lomustine, and prednisone for relapsed or refractory canine lymphoma

BACKGROUND: Canine lymphoma (LSA) is responsive to initial treatment, however, it then becomes resistant to drugs in the initial protocol. New rescue protocols are needed. HYPOTHESIS: A combination of L-asparaginase, lomustine, and prednisone will be well tolerated and efficacious as a rescue therapy for dogs with LSA. ANIMALS: Thirty-one client owned dogs with cytologically confirmed multicentric LSA who were refractory or whose disease had relapsed after a CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-based chemotherapy protocol. METHODS: Prospective clinical trial. Lomustine (target dose, 70 mg/m2) was administered orally at 3-week intervals for a total of 5 doses or until disease progression. L-asparaginase (400 U/kg) was administered subcutaneously concurrently with the first 2 lomustine treatments. Prednisone was administered at a tapering dose for the duration of the protocol. RESULTS: Overall response rate for dogs treated with this protocol was 87% (27/31), with 52% (16/31) of dogs achieving a complete response. Median time to response was 21 days. Median time to progression was 63 days (111 days for dogs achieving a complete response and 42 days for dogs achieving a partial response). There were no significant differences in response rates and times to progression between dogs who had received L-asparaginase before beginning this rescue protocol and those who had not. Toxicoses were mild and self-limiting in 29 of 31 cases. CONCLUSIONS AND CLINICAL IMPORTANCE: This is a well-tolerated rescue therapy for relapsing LSA in dogs. Response rates and remission durations compare favorably to other rescue protocols. Therefore, this protocol is a viable rescue option.     

Intestinal parasite infections in dogs affected by multicentric lymphoma and undergoing chemotherapy

Prevalence and species composition of intestinal parasites were evaluated in dogs affected by high-grade multicentric lymphoma and undergoing chemotherapy and in control healthy dogs. Obtained data were statistically analyzed. The overall prevalence of intestinal parasite infections was 33.3%. In lymphoma dogs, the prevalence of protozoa infections (46.7%) was significantly higher (p < 0.05) than that of helminth infections (6.7%) and Giardia duodenalis, Cryptosporidium spp., Neospora caninum, Cystoisospora ohioensis-complex, Entamoeba sp. and Spirocerca lupi were identified. In the control group, only 3/15 dogs (20%) were found positive and no statistically significant differences emerged regarding helminth (hookworms and Toxocara canis) and protozoa (G. duodenalis) infections. Results from this study may suggest a potential higher prevalence of opportunistic intestinal protozoa, including some potentially zoonotic species, in dogs affected by high-grade multicentric lymphoma, emphasizing the need to monitor lymphoma-affected dogs for these protozoa, especially those undergoing chemotherapy.     

Oncolytic reovirus therapy: Pilot study in dogs with spontaneously occurring tumours

Oncolytic virotherapy is a novel treatment involving replication‐competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 10⁸ to 5.0 × 10⁹ TCID₅₀ given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group‐ Common Terminology Criteria for Adverse Events (VCOG‐CTCAE) v1.1 guidelines. Viral shedding, neutralizing anti‐reovirus antibody (NARA) production and immunohistochemical (IHC) detection of reovirus protein in the tumours were also assessed. AE was not observed in most dogs and events were limited to Grade I or II fever, vomiting, diarrhoea and inflammation of the injected tumour. No infectious virus was shed and all dogs had elevated NARA levels post‐treatment. Although IHC results were only available in 6 dogs, 4 were detected positive for reovirus protein. In conclusion, reovirus is well‐tolerated and can be given safely to tumour‐bearing dogs according to the dosing regimen used in this study without significant concerns of viral shedding. Reovirus is also potentially effective in various types of canine tumours.     

Hematological toxicity of doxorubicin-containing protocols in dogs with spontaneously occurring malignant tumors

The medical records of 49 dogs with spontaneously occurring malignant tumors treated with doxorubicin-based chemotherapy protocols were evaluated for hematological toxicity. Protocols included vincristine, doxorubicin, and cyclophosphamide (VAC); 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); doxorubicin and cyclophosphamide (AC); and doxorubicin and dacarbazine (ADIC). Prevalence of Grades 1, 2, or 3 toxicities were less than 30%, and the prevalence of Grade 4 toxicity alone was less than 5%. The frequency of sepsis was less than 2.5% in dogs treated with VAC, FAC, or AC, and it was 15% in dogs treated with ADIC. There were no significant differences in the prevalence or severity of hematological toxicity caused by VAC or AC. Five-fluorouracil, doxorubicin, and cyclophosphamide caused significantly more severe neutropenia than VAC or AC. The low prevalence of hematological complications makes these protocols acceptable for use in practice.     

Unusual dermatological toxicity of hydroxyurea in two dogs with spontaneously occurring tumours

Hydroxyurea is a chemotherapeutic agent used to treat hypereosinophilic syndrome, mast cell tumours and many myeloproliferative disorders. It is usually well tolerated; however, reported side effects include myelosuppression and gastrointestinal complications as well as cutaneous toxicity, in very rare cases. We report the unusual appearance of onychomadesis involving several claws on all feet in two canine patients receiving long-term hydroxyurea treatment. The healing of nail lesions required cessation of treatment in one dog and dose reduction in the second animal, supporting a strict relationship between onychopathy and administration of hydroxyurea. The aim of this case report is to increase clinical awareness of dermatological toxicity associated with long-term administration of hydroxyurea.     

Impact of chemotherapeutic dose intensity and hematologic toxicity on first remission duration in dogs with lymphoma treated with a chemoradiotherapy protocol

BACKGROUND: Dose intensity has proven to be critical in maximizing chemotherapeutic efficacy for numerous human cancers. To date, the impact of dose intensity and toxicity on first remission duration has not been thoroughly assessed in dogs with lymphoma. HYPOTHESIS: Dogs that receive maximal dose intensity will have prolonged first remission duration. ANIMALS: Sixty-two dogs with lymphoma that were treated according to a standardized chemoradiotherapy regimen and achieved durable complete remissions were identified from the medical records database of North Carolina State University. METHODS: Dosage reductions and treatment delays resulting from chemotherapy-related neutropenia were evaluated retrospectively, and each patient's actual summation dose intensity and frequency of myelotoxicity were calculated. Impact of dose intensity and frequency of neutropenia on first remission duration were evaluated by Cox proportional hazards regression. RESULTS: Development of grade III or IV neutropenia during chemotherapy was found to be associated with prolonged first remission duration (P < .01). Dose intensity did not have a significant impact on remission duration (P = .07). CONCLUSIONS AND CLINICAL IMPORTANCE: Results of this study suggest that dosage reductions and treatment delays instituted to avoid repeated neutropenic episodes do not reduce first remission duration. Prolonged remission duration in patients that developed grade III or IV neutropenic episodes indicates the need for further optimization of dosing strategies for canine lymphoma patients undergoing chemotherapy.     

Use of mycophenolate mofetil as a rescue agent in the treatment of severe generalized myasthenia gravis in three dogs

Objective – To describe the use of IV and oral mycophenolate mofetil (MMF) as adjunctive therapy in 3 dogs with severe generalized myasthenia gravis.
Case Series Summary – Three dogs suffering from severe generalized myasthenia gravis as confirmed by acetylcholine antibody titers were treated with MMF as part of their treatment regimens. All 3 dogs had radiographic evidence of megaesophagus and suffered from severe regurgitation. Each dog was initially treated with pyridostigmine and supportive agents. When clinical remission was not achieved, IV MMF was administered to all dogs. Signs of clinical remission were apparent within 48 hours and all dogs were later maintained on oral MMF following resolution of regurgitation.
New or Unique Information Provided – This is the first report of the use of IV MMF as adjunctive treatment in dogs with severe generalized myasthenia gravis. Outcome was favorable in all 3 dogs and no adverse effects were noted from the MMF.     

The immunophenotype of peripheral blood lymphocytes in clinically healthy dogs and dogs with lymphoma in remission

Lymphoma is a common cancer of dogs that frequently is treated with chemotherapy or radiation therapy. Response to therapy is variable and currently available diagnostic tests do not reliably predict response to therapy. Treatment for lymphoma often results in lymphopenia, but it is unknown whether the changes in circulating lymphocytes result from generalized or specific reduction of lymphocytes. In this study, blood lymphocytes from 12 clinically healthy dogs, 10 dogs in remission because of treatment for B-cell lymphoma, and 8 dogs in remission from T-cell lymphoma were analyzed by flow cytometry by using a panel of 20 antibodies reactive with canine leukocyte antigens. Results identified similar lymphocyte parameters in treated dogs regardless of the type of lymphoma. Treated dogs had >50% reduction in blood lymphocyte concentration, and an absolute decrease in most subsets of lymphocytes. Both groups of treated dogs had relative increases in the proportion of CD3+, T-cell receptor (TCR)αβ+, and CD90+ lymphocytes, and a decreased proportion of CD45RA+ cells. In addition, dogs with T-cell lymphoma in remission had a significant increase in the proportion of CD49d+ lymphocytes. These findings were interpreted as representing likely suppression of lymphocyte regeneration by chemotherapy, with a relative increase in the proportion of memory over naïve lymphocytes. Lack of correlation with the T- or B-cell origin of the initial lymphoma suggested that, by using flow cytometric methods, residual circulating neoplastic cells could not be detected. However, the changes in the lymphocyte profile of dogs treated with chemotherapy may have relevance to their immunocompetence.     

Adjuvant carboplatin and gemcitabine combination chemotherapy postamputation in canine appendicular osteosarcoma

Background: Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low‐dosage (10 mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective: The purpose of the following study was to determine whether the addition of low‐dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals: Fifty dogs with histologically confirmed appendicular OSA. Methods: Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results: The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease‐free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1‐ and 2‐year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P= .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance: These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.     

Combination chemotherapy in feline lymphoma: treatment outcome, tolerability, and duration in 23 cats

BACKGROUND: Different chemotherapy regimes have been described for feline lymphoma with varying outcomes. HYPOTHESIS: In cats with lymphoma, a long-term, multiagent chemotherapy protocol will be effective and carry acceptable toxicity. ANIMALS: Twenty-three cats with histologically or cytologically confirmed diagnosis of lymphoma. METHODS: Prospective, single-arm clinical trial in which cats were treated with a chemotherapy protocol consisting of a cyclic combination of l-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone with a planned total treatment time of 122 weeks. RESULTS: Complete remission (CR) rate was 74% (n = 17). Fourteen percent of cats attained partial remission (PR). Median duration of first CR was 264 days (range, 45-2,485 days). Six-month, 1-, and 2-5-year remission rates were 75, 50, and 34%, respectively. Duration of PR ranged between 23 and 63 days. Median survival in cats with CR was 296 days (range, 50-2,520 days). Six-month, 1-, 2-, and 3-5-year survival rates in cats with CR were 82, 47, 34, and 27%, respectively. Survival of cats achieving PR ranged between 38 and 120 days. Of the analyzed variables, only anatomical location had a significant influence on remission duration (P=.022). Actual median treatment time in cats with CR was 128 days (18 weeks). Hematologic and gastrointestinal toxicosis was infrequent and mostly low grade. CONCLUSIONS AND CLINICAL IMPORTANCE: In this population of cats with lymphoma, chemotherapy was effective. With infrequent and mostly low-grade toxicosis, tolerability of the protocol may be considered good.