The efficacy and adverse event profile of dexamethasone,melphalan, actinomycin D,and cytosine arabinoside (DMAC) chemotherapy in relapsed canine lymphoma

In this retrospective study, a chemotherapy protocol using dexamethasone, melphalan, actinomycin D, and cytosine arabinoside (DMAC) was evaluated for efficacy and adverse event profile as a first line rescue protocol in 86 client-owned dogs previously treated with a CHOP-based protocol. Forty-three dogs (43%) achieved remission (16% complete remission, 27% partial remission), and 57% were non-responders. The median overall progression-free survival (PFS) was 24 days. Adverse events included thrombocytopenia in 41% of dogs, neutropenia in 17% of dogs, and gastrointestinal toxicity in 13% of dogs. Overall, 16% (13/79) dogs experienced grade III to IV thrombocytopenia, 8% (6/74) dogs grade III to IV neutropenia and 1% (1/79) dogs grade III to IV gastrointestinal toxicity. The efficacy of the DMAC protocol is similar to that of other rescue protocols in dogs with relapsed lymphoma but is associated with shorter PFS. The main toxicity is thrombocytopenia, which may limit treatment.     

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.     

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.     

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.     

Mechlorethamine,vincristine, melphalan and prednisone (MOMP) for the treatment of relapsed lymphoma in dogs

Eighty‐eight dogs with relapsed lymphoma were treated with the MOMP (mechlorethamine, vincristine, melphalan and prednisone) protocol on a 28‐day treatment cycle. The overall response rate (ORR) to the MOMP protocol was 51.1% for a median of 56 days (range 7–858 days). Twelve percent of dogs experienced a complete response for a median of 81 days (range 42–274 days) and 38.6% experienced a partial response for a median of 49 days (range 7–858 days). Dogs with T‐cell lymphoma had an ORR of 55% for a median of 60 days (range 49–858 days) while those with B‐cell lymphoma had an ORR of 57% for a median of 81 days (range 7–274 days) (P = 0.783). The overall survival time for all dogs was 183 days (range 17–974 days). Fifty‐four percent of dogs experienced toxicity with the majority classified as grade I. The MOMP protocol seems well‐tolerated and is an option for dogs with relapsed lymphoma.     

Single agent gemcitabine chemotherapy in dogs with spontaneously occurring lymphoma

BACKGROUND: Gemcitabine has been shown to be effective as a single agent in a variety of tumors including nonHodgkin's lymphoma. Its use in veterinary medicine has been limited and to date this drug has not been used as a first-line therapy in dogs with lymphoma. HYPOTHESIS: Gemcitabine as a single agent may be efficacious in dogs presented for the first time with lymphoma. ANIMALS: Twenty-four dogs with spontaneously occurring lymphoma. METHODS: All dogs were clinically staged and given gemcitabine at 400 mg/m(2) over a 30-minute intravenous infusion weekly for 3 weeks and then given 1 week off treatment before starting a second cycle. RESULTS: A single dose of gemcitabine lowered both neutrophil count (decrease in mean neutrophil count from 10,640 cells/ microL to 3,140 cells/microL) and platelet count (decrease in mean platelet count from 201,290 cells/microL to 139,190 cells/microL) 7 days after administration. Consequently gemcitabine dosage was reduced at the second treatment in 8 of 21 dogs or a dose delay of 1-7 days and a reduction of dosage was used in 7 of 21 dogs. Seven dogs completed the assigned 4-week cycle. Two of these dogs had progressive disease and 5 had stable disease. No objective responses were seen in dogs treated with a second cycle of gemcitabine. CONCLUSIONS AND CLINICAL IMPORTANCE: Gemcitabine administration as a single agent resulted in hematologic toxicity and did not reduce lymphoma burden. If gemcitabine is to be used in veterinary medicine, additional prospective pharmacologic studies should be done to determine the appropriate dosage, regimen, and schedule of use before it can be recommended for use in the treatment of dogs with lymphoma as a single agent.     

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.     

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.     

Treatment of dogs with lymphoma using a 12-week, maintenance-free combination chemotherapy protocol

BACKGROUND: Treatment of lymphoma in dogs by long-term chemotherapy has favorable results. However, the efficacy of short-term, maintenance-free treatment protocols on remission and survival times in dogs has not been determined. HYPOTHESIS: That treatment using a 12-week chemotherapy protocol would be associated with satisfactory treatment outcome in dogs with lymphoma. ANIMALS: 77 dogs with histologically or cytologically confirmed diagnosis of lymphoma. METHODS: Prospective clinical trial in which dogs were treated with a 12-week chemotherapy protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisolone. RESULTS: Complete remission rate was 76.3%. Multivariate logistic regression analysis revealed that clinical substage (P = .006) and immunophenotype (P = .003) had a significant influence on the likelihood of a dog achieving complete remission. Median duration of first complete remission was 243 days (range 19-1,191 days). The 6-month, 1-year, and 2-year remission rates were 68%, 28%, and 16%, respectively. In the multivariate analysis of patient variables, immunophenotype (P = .022) revealed a significant influence on first remission duration. Toxicosis was mild with the exception of 1 treatment-associated death. CONCLUSIONS AND CLINICAL IMPORTANCE: In this group of dogs the 12-week maintenance-free chemotherapy protocol was well tolerated and had satisfactory results.     

Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma

Background

Idarubicin, a PO bioavailable anthracycline antibiotic‐class chemotherapeutic, could have substantial convenience advantages over currently available similar class agents in use that require IV delivery.

Objectives

The primary objective of this study was to determine the maximally tolerated dose (MTD), dose‐limiting toxicities (DLTs), and basic pharmacokinetic parameters of oral idarubicin exposure in dogs with lymphoma after a single oral dose. A secondary objective was to document preliminary antitumor efficacy in an expanded treatment cohort using the established MTD.

Animals

Client‐owned dogs with measurable lymphoma.

Methods

Dogs (n = 31) were enrolled in a prospective open label phase I study of oral idarubicin. By means of a 3 + 3 cohort design, dose escalations were made with 3 dogs per dose level, and the MTD was established based on the number of patients experiencing a DLT. Plasma concentrations of idarubicin and idarubicinol were determined by postdose sampling. Assessment of antitumor efficacy focused on evaluation of accessible, measurable lymph nodes and skin lesions by modified RECIST guidelines.

Results

The MTD in dogs > 15 kg body weight was 22 mg/m². Adverse hematologic events (neutropenia and thrombocytopenia) were the predominant DLT and generally correlated with higher plasma concentrations of idarubicin and idarubicinol.

Conclusions and Clinical Importance

PO administered idarubicin was generally well‐tolerated and had preliminary antitumor activity in dogs with lymphoma. Furthermore, the potential clinical advantage of a safe and efficacious oral anthracycline alternative supports further investigations of this agent in repeated‐dose, randomized clinical trials.     

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.     

Evaluation of a discontinuous treatment protocol (VELCAP-S) for canine lymphoma

Eighty-two dogs with lymphoma received a single 15-week course of chemotherapy, after which treatment was ceased until relapse. Fifty-six dogs (68%) achieved complete remission for a median 1st remission duration of 20 weeks. Forty-eight dogs relapsed, of which 30 repeated the induction cycle. In 22 of these dogs, 1st remission had been short, and they received maintenance chemotherapy; the other 8 dogs received 2 or 3 cycles of induction chemotherapy. Second remission rate for these 30 dogs was 87% (26 dogs). Overall disease control for the 38 dogs that remained on protocol was 44 weeks, which was not markedly shorter than for dogs treated with a previously reported protocol in which maintenance chemotherapy was instituted in all dogs after an identical 1st induction (VELCAP-L). Dogs that were febrile and dogs that were dyspneic were less likely to achieve a complete remission to induction chemotherapy. Of dogs that achieved a complete remission, those that were thrombocytopenic at entry had a shorter 1st remission, and dogs that were anorexic at entry had shorter overall disease control. There was a correlation between 1st remission duration and length of any subsequent remission obtained. The incidence of toxicity was high, particularly after the combination of doxorubicin and vincristine. Dose reductions because of toxicity did not markedly reduce remission duration. We conclude that discontinuous chemotherapy may reduce patient visits in a small number of patients because of long-term disease control. Delaying maintenance chemotherapy until after 2nd remission is achieved does not markedly affect overall disease control.     

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.     

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.     

Splenic marginal zone lymphoma in 5 dogs (2001-2008)

Background: Splenic marginal zone lymphomas (MZL) in dogs arise from the marginal zone of B‐cell follicles and can progress slowly. Objectives: To describe clinical features, treatment, and outcome of dogs with splenic MZL. Animals: Five dogs with naturally occurring MZL. Methods: Clinical, laboratory, and follow‐up data were retrospectively reviewed. Diagnosis was based on clinical, histopathological, and immunophenotypic features. Results: All dogs had stage IV disease; among them, 2 were symptomatic (substage “b”) because of splenic rupture. Four dogs underwent splenectomy and adjuvant doxorubicin, and 1 dog underwent surgery only. Three out of the 4 dogs treated with surgery and chemotherapy died of causes unrelated to lymphoma, after 760, 939, and 1,825 days, whereas the remaining dog was alive and in complete remission after 445 days. The dog not receiving any adjuvant treatment had recurrence of the tumor after 180 days. Conclusions and Clinical Importance: Splenic MZL appears indolent and can benefit from splenectomy, with or without systemic chemotherapy.     

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.     

Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker for prognosis and monitoring the disease

Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lymphoma (ML). The objective was to investigate if sTK, as in humans, could be used as a prognostic marker for survival time in dogs with ML and if sTK could identify early signs of progression of disease in treated dogs. Serum samples from 52 dogs with ML were tested for initial TK activity. Samples from 21 normal dogs and 25 dogs with nonhematologic neoplasms were used for comparison. Forty-four dogs with ML were treated. Serum TK activity was measured in treated dogs before each treatment and every 4 weeks thereafter until relapse. Dogs with ML had 2-180 times higher TK activity (TK 5-900 U/L) than normal dogs (TK <7 U/L) based on the mean + 2 standard deviations. In the group of other neoplasms, only 2 dogs had a moderate increase (6.4 and 7.5 U/L) compared with the controls. Mean sTK activities in the dogs with ML that had gone into complete remission (CR) were not significantly different from activities in healthy controls (P = .68). Mean sTK at least 3 weeks before and at the time of relapse was significantly higher than activity measured at CR (P < .0001). Dogs with ML that initially had sTK >30 U/L had significantly shorter survival times (P < .0001). Furthermore, sTK activity reflected the clinical staging of ML. Measuring sTK can be used as a powerful objective tumor marker for prognosis and for predicting relapse before recurrence of clinically detectable disease in dogs with ML undergoing chemotherapy.     

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], 14–50%) for a median of 96 days (95% CI, 55–137 days). Three dogs (1 disseminated, 2 localized) had complete responses lasting for 54–269 days and 3 dogs (2 disseminated, 1 localized) had partial responses lasting for 78–112 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.     

Actinomycin D as rescue therapy in dogs with relapsed or resistant lymphoma: 49 cases (1999--2006)

OBJECTIVE: To evaluate response rate and disease-free interval in dogs with relapsed or resistant lymphoma treated with actinomycin D, determine hematologic toxicoses, and identify prognostic factors associated with response to treatment. DESIGN: Retrospective case series. ANIMALS: 49 dogs with relapsed or resistant lymphoma. PROCEDURES: Medical records were reviewed for information regarding signalment, physical examination findings, results of diagnostic testing, substage, previous chemotherapy, previous treatment with prednisone, actinomycin D dosage, number of doses administered, response, disease-free interval, and results of CBCs performed after treatment. RESULTS: Actinomycin D was administered at a median dosage of 0.68 mg/m2 (range, 0.46 to 0.72 mg/m2), IV, every 3 weeks for 5 treatments or until disease progression. Twenty-six (53%) dogs received prednisone concurrently. Twenty (41%) dogs had a complete remission, and median disease-free interval in these dogs was 129 days. Thrombocytopenia was the most common hematologic toxicosis (n = 22 [45%]). Concurrent prednisone administration, a shorter duration of first remission, and an increased number of previous chemotherapy agents were significantly associated with a lower likelihood of responding to actinomycin D treatment. Concurrent prednisone administration and an increased number of previous chemotherapy agents were significantly associated with a shorter disease-free interval. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that administration of actinomycin D as a single agent was effective for rescue chemotherapy of dogs with relapsed or resistant lymphoma and that treatment was well tolerated, although mild thrombocytopenia developed commonly.     

A dexamethasone,melphalan, actinomycin‐D and cytarabine chemotherapy protocol as a rescue treatment for feline lymphoma

Nineteen cats with relapsed high‐grade/large‐cell lymphoma were treated with dexamethasone, melphalan, actinomycin‐D and cytarabine (DMAC). All cats had received Cyclophosphamide, Vincristine, Prednisolone (COP) as first‐line chemotherapy and most cats had received at least 2 prior rescue agents with 14 of 19 having received both epirubicin and lomustine. Five cats (26%) exhibited a response (defined as an improvement or resolution of tumour‐associated clinical signs/tumour volume, or complete/partial response) to chemotherapy though no patients received more than 2 cycles of DMAC. Most cats tolerated the protocol well though 3 patients exhibited Veterinary Cooperative Oncology Group (VCOG) grade 4 neutropenia and 1 patient exhibited grade 4 thrombocytopenia. The median progression‐free survival and overall survival from starting DMAC were 14 and 17 days respectively. There is still an unmet need for successful rescue chemotherapy protocol for cats with relapsed lymphoma. [Correction added on 02 November 2017, after first online publication: The expansion for the term DMAC was previously incorrect and has been corrected in this current version.]