Chemotherapy with cyclophosphamide, vincristine, and prednisolone (COP) in cats with malignant lymphoma: new results with an old protocol

This retrospective study in 61 cats with malignant lymphomas examined the efficacy of a well-established chemotherapy protocol (cyclophosphamide, vincristine, and prednisolone [COP]) in the Netherlands, a country with a low prevalence of feline leukemia virus (FeLV). Twenty-two cats (36.1%) had mediastinal lymphoma, 11 (18.0%) had alimentary lymphoma, 7 (11.5%) had peripheral lymphoma, 8 (13.1%) had nasal lymphoma, and 13 (21.3%) had miscellaneous lymphoma (including renal lymphoma in 2 [3.3%]). Of the 54 cats that were tested, only 4 (7.4%) were FeLV positive. Complete remission (CR) was achieved in 46 of the 61 cats (75.4%). The estimated 1- and 2-year disease-free periods (DFPs) in the 46 cats with CR were 51.4 and 37.8%, respectively, whereas the median duration of remission was 251 days. The overall estimated 1-year survival rate in all cats was 48.7%, and the 2-year survival rate was 39.9%, with a median survival of 266 days. The median survival time and the 1-year survival rate for mediastinal lymphoma were 262 days and 49.4%. respectively. Siamese cats had a more favorable prognosis for survival and remission than other breeds. Response to therapy in this study was shown to be a significant prognostic indicator. CR is necessary for long-term survival. Cats that did not achieve CR had little chance of survival for longer than I year. Young Siamese cats in this study had a greater tendency to develop mediastinal malignant lymphoma at a young age, and all were FeLV negative. In comparison with results reported in other studies with different combination chemotherapy protocols, these are among the highest percentages of remission and the longest survival rates for cats with malignant lymphoma.     

CHEMOTHERAPY FOLLOWED BY ABDOMINAL CAVITY IRRADIATION FOR FELINE LYMPHOBLASTIC LYMPHOMA

Combination chemotherapy is standard care for feline lymphoma, although clinically relevant improvements in remission duration are unlikely to result from manipulations of chemotherapy agents alone. Lymphopoietic tissues generally are sensitive to radiation, and support for chemoradiotherapy as a treatment for lymphoma is found in both humans and dogs. The goal of this prospective pilot study was to determine the normal tissue tolerance to 15 Gy total abdomen fractionated radiation therapy following induction chemotherapy in cats with lymphoblastic lymphoma. Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6‐week combination chemotherapy protocol followed 2 weeks later by whole‐abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons; no evidence of lymphoma or radiation toxicoses was identified on post mortem evaluation. The remaining five cats remain in remission at least 266 days after starting therapy; median remission duration has not been reached (range, >266 to >1332 days). Results of this study suggest that 15 Gy total abdomen fractionated radiation therapy after induction chemotherapy is tolerated satisfactorily. This protocol is suitable for further testing to quantify efficacy.     

Feline discrete high‐grade gastrointestinal lymphoma treated with surgical resection and adjuvant CHOP‐based chemotherapy: retrospective study of 20 cases

The aim of this retrospective study was to evaluate the outcome of cats treated with surgical intervention for a discrete intermediate‐/high‐grade gastrointestinal lymphoma prior to CHOP‐based chemotherapy. Variables including sex, breed, haematocrit, white blood cell count, serum albumin concentration, clinical stage of disease, gastrointestinal obstruction and peritonitis were assessed for their effect on survival. Twenty cats met the inclusion criteria with three cats still alive at the time of data analysis. The overall median survival time (MST) was 417 days (range: 12–2962 days). The disease‐free interval (DFI) was 357 days (range: 0–1585 days) with six cats still deemed in remission prior to death. Only clinical stage had a significant effect on both MST and DFI. Cats with discrete intermediate/high‐grade gastrointestinal lymphoma that undergo surgical resection followed by adjuvant CHOP chemotherapy may achieve acceptable overall survival times.     

RESPONSE OF NINETEEN CATS WITH NASAL LYMPHOMA TO RADIATION THERAPY AND CHEMOTHERAPY

The records of 19 cats treated for stage I nasal lymphoma with radiation therapy and chemotherapy were reviewed to determine response to therapy, treatment outcome and possible prognostic indicators. All cats were treated with megavoltage radiation therapy to a total dose ranging from 22 to 48 Gy (median dose = 42 Gy). All cats were prescribed at least 6 months of multiagent chemotherapy. The median progression-free interval for all cats was 945 days (31 months). Two cats did not achieve clinical remission. Of 17 cats evaluable for relapse, 10 (58.8%) were progression free during the entire follow-up period. Four cats (23.5%) suffered local recurrence, while three (17.6%) experienced distant relapse. The median survival time was 955 days (31.4 months). The only variable found to have a significant negative impact on survival was destruction of the cribriform plate before therapy (P= 0.002). The long progression free and survival times reported here indicate that cats with stage I nasal lymphoma treated with aggressive local and systemic therapy can have a favorable outcome when compared with other anatomic forms of lymphoma. Despite strong clinical responses to the multimodality therapy used, the fact that three (17.6%) cats relapsed distantly supports the recommendation that treatment with radiation therapy alone is insufficient until further prospective studies can be performed.     

Gemcitabine as a radiosensitizer for nonresectable feline oral squamous cell carcinoma

Eight cats with locally advanced, oral squamous cell carcinoma (SCC) were treated with a combination of gemcitabine and palliative radiotherapy. Low-dose gemcitabine was administered twice weekly (25 mg/m2) in conjunction with megavoltage radiation in 6 Gray (Gy) fractions for a total dose of 36 Gy. Responses included two complete and four partial responses, and two cats had no response to therapy. Median duration of remission was 42.5 days (range, 11 to 85 days). Median survival time was 111.5 days (range, 11 to 234 days). This data suggests that a combination of low-dose gemcitabine and palliative radiation therapy may be tolerable for cats with oral SCC and may cause a therapeutic benefit.     

Outcome of stereotactic body radiation for treatment of nasal and nasopharyngeal lymphoma in 32 cats

BackgroundThe safety and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of localized nasal lymphoma in cats has not been described.HypothesisStereotactic body radiation therapy with or without adjuvant chemotherapy is an effective and well‐tolerated treatment for localized nasal lymphoma in cats.AnimalsThirty‐two client owned cats referred to Colorado State University for the treatment of nasal lymphoma.MethodsRetrospective study of cats treated with SBRT between 2010 and 2020 at Colorado State University. Diagnosis of nasal lymphoma was obtained via cytology or histopathology. Signalment, radiation protocol, concurrent treatments, adverse effects, and survival were recorded.ResultsProgression free survival was 225 days (95% CI 98–514) and median survival time (MST) was 365 days (95% CI 123–531). No significant difference in survival was identified between cats that received 1 versus greater than 1 fraction (MST 427 vs. 123 days, P = 0.88). Negative prognostic factors included cribriform lysis (MST 121 vs. 876 days, P = 0.0009) and intracalvarial involvement (MST 100 vs. 438 days, P = 0.0007). Disease progression was noted in 38% (12/32), locally in 22% (7/32), and systemically in 16% (5/32). No cats developed acute adverse effects. Ten cats developed late adverse effects: keratitis/keratitis sicca (n = 2), alopecia (n = 4), and leukotrichia (n = 4). Twenty‐four cats (75%) had signs consistent with chronic rhinitis.ConclusionsSBRT is effective and well tolerated for treating localized nasal lymphoma in cats. Outcomes for cats with lower stage disease (canine modified Adam''s stage 3 and lower) are comparable to historic data of cats treated with fractionated radiation therapy.     

PALLIATIVE RADIATION THERAPY OUTCOMES FOR CATS WITH ORAL SQUAMOUS CELL CARCINOMA (1999–2005)

Squamous cell carcinoma (SCC) accounts for approximately 10% of all feline tumors. The purpose of this retrospective study was to describe outcomes for a group of cats with oral SCC that were treated with palliative radiation therapy. Fifty‐four cats met the inclusion criteria of nonresectable, oral SCC treated with coarse fractionated megavoltage (MeV) radiation therapy. Radiation therapy for all cats was delivered with a 6 MeV linear accelerator. Total radiation doses of 24 Gray to 40 Gray were administered in three to four fractions, once‐per‐week over 4 to 5 weeks. Concurrent chemotherapy protocols varied and were administered at the discretion of the clinician and client. Forty‐nine patients completed the planned treatment protocols. Overall mean and median survival times for cats completing the planned treatment protocols were 127 and 92 days (n = 49). Mean and median survival times of cats receiving palliative radiation therapy alone were 157 and 113 days (n = 12). Mean and median survival times of patients receiving both radiation therapy and chemotherapy were 116 and 80 days (n = 37). Patients with sublingual tumors had a median survival time of 135 days (n = 15), compared to mandibular tumors that had a median survival time of 80 days (n = 26). For the majority of patients that completed the planned treatment protocol (65%), owners reported a subjectively improved quality of life. Findings from this uncontrolled study supported the use of palliative radiation therapy for cats with nonresectable oral squamous cell carcinoma.     

Evaluation of P-glycoprotein expression in feline lymphoma and correlation with clinical outcome

P-glycoprotein (Pgp) is a transmembrane protein pump involved in drug resistance in canine and human lymphoma. There are no published clinical studies evaluating Pgp expression in feline lymphoma. The purpose of this study is to evaluate the level of Pgp expression in feline lymphoma and correlate it with clinical outcome. Two human Pgp monoclonal antibodies, C219 and C494, were used to detect Pgp expression in tissue samples from 63 cats with lymphoma. Demographic results appear comparable to recently published feline lymphoma studies. The Kaplan–Meier median remission and survival times were 164 and 571 days, respectively. Fourteen cats had positive expression of Pgp using MAb C219, and 40 were positive with C494. Variables statistically associated with survival included bone marrow involvement, stage, substage, and use of radiation therapy as a part of treatment. Pgp expression as assessed by MAb C219 and C494 is not predictive of remission or survival time in cats with lymphoma.     

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.     

Survival Analysis of 97 Cats with Nasal Lymphoma: A Multi-Institutional Retrospective Study (1986–2006)

Background: Feline nasal lymphoma (NLSA) is a condition for which no standard of care exists.
Hypothesis: There is no difference in survival times of cats with NLSA treated with single or multimodality therapy.
Animals: Records from 97 cats diagnosed with NLSA were examined.
Methods: The purpose of this retrospective study was to compare the survival times of cats with NLSA treated with radiation therapy (RT) alone, chemotherapy alone, or RT + chemotherapy and identify potential prognostic variables that affected survival. Cats were grouped according to therapy: RT + chemotherapy (n = 60), RT alone (n = 19), or chemotherapy alone (n = 18).
Results: Survival was calculated with 2 methods. The 1st survival analysis (method A) included all cats, but counted only deaths caused by progressive NLSA. The median survival time (MST), regardless of therapy modality, was 536 days. The 2nd survival analysis (method B) also included all cats and counted all deaths, regardless of cause, as events. The overall MST calculated for all deaths was 172 days. A negative independent prognostic variable identified was anemia ( P < .001), and positive independent prognostic variables were a complete response to therapy ( P < .001) and total radiation dose >32 Gy ( P = .03).
Conclusions and Clinical Importance: There were no significant differences in survival times among the 3 treatment groups but these results suggest that the addition of higher doses of RT to a cat's treatment protocol may control local disease and therefore influence survival.     

Feline exocrine pancreatic carcinoma: a retrospective study of 34 cases

Thirty‐four cases were reviewed in this retrospective study for information on clinical presentation, prognostic indicators, survival time and response to various therapies. The most common presenting clinical signs were weight loss, decreased appetite, vomiting, palpable abdominal mass and diarrhoea. Metastatic disease was confirmed in 11 cats. The overall median survival was 97 days. The median survival times for patients who received chemotherapy or had their masses surgically removed was 165 days. Those patients who had an abdominal effusion present at the time of diagnosis survived a median of 30 days. Cats that received non‐steroidal anti‐inflammatory drug therapy had a median survival of 26 days. This study confirms that exocrine pancreatic carcinoma in cats is an aggressive tumour with a high metastatic rate and poor prognosis, although three patients survived over 1 year. Fifteen percent of the patients were diabetic, which raises the question as to what the link between diabetes and pancreatic cancer in people and cats may be.     

Feline large granular lymphocyte lymphoma: An Italian Society of Veterinary Oncology (SIONCOV) retrospective study

Feline large granular lymphocyte (LGL) lymphoma is an uncommon subtype of lymphoma characterized by a grave prognosis and scarce response to chemotherapy. There are limited reports on clinico‐pathological and prognostic factors. One‐hundred and 9 cats with newly diagnosed LGL lymphoma that underwent initial staging (including hematology, serum biochemistry, thoracic radiographs and abdominal ultrasound), and followed‐up were retrospectively evaluated. LGL lymphoma was localized within the gastrointestinal tract with or without extra‐intestinal involvement in 91.7% of the cases, and at extra‐gastrointestinal sites in 8.3%. Symptoms were frequent. Anemia (31.2%) and neutrophilia (26.6%) were commonly observed, and 14 (12.8%) cats had neoplastic circulating cells. Frequent biochemistry abnormalities included elevated ALT (39.4%) and hypoalbuminemia (28.4%). Twenty (54.1%) of 37 cats had elevated serum LDH. Treatment varied among cats, and included surgery (11%), chemotherapy (23%), corticosteroids (38.5%) and no treatment (27.5%). Median time to progression (MTTP) was 5 days, and median survival time (MST) 21 days. MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response. A small subset of cats (7.3%) survived more than 6 months, suggesting that a more favorable clinical course can be found among LGL lymphoma patients.     

RADIOTHERAPY AND SURGERY FOR FELINE SOFT TISSUE SARCOMA

Medical records for 79 cats with soft tissue sarcomas treated with preoperative or postoperative curative intent radiation therapy between August 1994 and February 2004 were reviewed. The purpose was to assess the effectiveness of preoperative and postoperative radiation therapy, and to determine the association of patient and radiation treatment variables with survival. Gender, age, weight, anatomic tumor site, packed cell volume (PCV), computerized vs. manual treatment planning, radiation field length, preoperative vs. postoperative irradiation, total radiation dose, and biologically effective dose (BED) were assessed as prognostic factors for survival. Fifty-six of 79 (71%) of cats were anemic within 2 weeks before or during radiation treatment. The median survival was 520 days for all cats, with a 1-year survival rate of 61.6%, and a 2-year survival rate of 41.6%. Only timing of radiation therapy relative to surgery and presence of a moderate or severe anemia were significantly related to survival. The median survival was 310 days for cats treated with preoperative radiation therapy, and 705 days for cats treated with postoperative radiation therapy ( P =0.03). The median survival was 308 days for cats with a PCV<25%, and 760 days for cats with a PCV≥25% ( P =0.017). Radiation therapy in combination with surgery results in relatively long-term survival in cats with soft tissue sarcomas. Anemia is common in cats undergoing radiation therapy for soft tissue sarcomas, and is associated with decreased survival.     

Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995-2005)

OBJECTIVE: To evaluate factors associated with response to treatment, remission duration, and survival in cats with low-grade lymphoma affecting various organ systems. DESIGN: Retrospective case series. Sample POPULATION: 41 cats with histologically confirmed low-grade lymphocytic lymphoma. PROCEDURES: Medical records and biopsy specimens of cats with histologically confirmed low-grade lymphocytic lymphoma of various organ systems treated with prednisone and chlorambucil between 1995 and 2005 were reviewed. The Kaplan-Meier method was used to estimate remission duration and survival. Factors potentially associated with prognosis were compared. RESULTS: Common clinical signs were weight loss (83%), vomiting (73%), anorexia (66%), and diarrhea (58%). Seventy-eight percent of cats tested had low serum cobalamin concentrations. Lymphoma was confined to the gastrointestinal tract in 68% of cats. Fifty-six percent of cats achieved a complete response to treatment, and 39% achieved a partial response. Five percent of cats had no response. No association was found between any risk factors (including anatomic site) and response to treatment. Partial response was associated with shorter remission duration, compared with complete response; median remission duration was 428 days for cats achieving a partial response, compared with 897 days for cats achieving a complete response. No other factors were associated with remission duration. Overall median survival time was 704 days. No factors were significantly associated with survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Most cats with lymphocytic lymphoma responded to treatment with prednisone and chlorambucil, and most factors evaluated were not associated with outcome.     

Hypofractionated radiation therapy of oral melanoma in five cats

Five cats with melanoma involving the oral cavity were treated with hypofractionated radiation therapy (RT). Cobalt photons were used to administer three fractions of 8.0 Gray (Gy) for a total dose of 24 Gy. Four cats received radiation on days 0, 7, and 21 and one cat received radiation on days 0, 7, and 13. One of the cats received additional irradiation following the initial treatment course. Two cats received chemotherapy. Their age ranged from 11 to 15 years with a median age of 12 years. Three cats had a response to radiation, including one complete response and two partial responses. All five cats were euthanized due to progression of disease, with one cat having evidence of metastatic disease at the time of euthanasia. The median survival time for the five cats was 146 days (range 66-224 days) from the start of RT. The results of this study suggest that oral melanoma in cats may be responsive to hypofractionated RT, but response does not seem to be durable.     

Feline extranodal lymphoma: response to chemotherapy and survival in 110 cats

O bjective : To determine response to treatment, survival and prognostic factors for feline extranodal lymphoma in the UK.
M ethods : Records of cats diagnosed with lymphoma of extranodal sites at seven referral centres were reviewed and information on signalment, tumour location, prior treatment and chemotherapy protocol recorded. Factors influencing response to treatment and survival were assessed.
R esults : One hundred and forty-nine cases met inclusion criteria. Sixty-nine cats had nasal lymphoma, 35 renal, 15 central nervous system, 11 laryngeal and 19 miscellaneous locations. Sixty-six cats received cyclophosphamide, vincristine, prednisolone, 25 Wisconsin-Madison doxorubicin-containing multi-agent protocol, 10 prednisolone alone and nine other combinations. The response rate for the 110 treated cats was 85·5 per cent. Of cyclophosphamide, vincristine, prednisolone treated cats 72·7 per cent achieved complete remission, median survival 239 days. Sixty-four per cent of Wisconsin-Madison treated cats achieved complete remission, median survival 563 days. Cats with nasal lymphoma achieving complete remission had the longest survival (749 days) and cats with central nervous system lymphoma the shortest (70 days). If complete remission was achieved, prior treatment with corticosteroids significantly reduced survival time.
C linical S ignificance : Cats with extranodal lymphoma respond to chemotherapy and achieve survival times comparable to other locations. Corticosteroid pretreatment reduced survival time in cats achieving complete remission.     

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.     

Feline Lymphoma (145 Cases): Proliferation Indices, Cluster of Differentiation 3 Immunoreactivity, and Their Association with Prognosis in 90 Cats

Paraffin-embedded, formalin-fixed tissue samples from 145 cats with lymphoma were analyzed for cluster of differentiation 3 (CD3, a surface antigen) immunoreactivity, argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). This information along with signalment, anatomic site, and feline leukemia virus (FeLV) antigen status was used to determine the potential of these indicators to predict response to therapy, remission, and survival times, and to characterize cats with lymphoma in the era of general availability of FeLV testing and vaccination. Alimentary lymphoma, primarily occurring in older, FeLV-negative cats, was the most common site of involvement. Although the majority of tumors from FeLV-positive cats were CD3-immunoreactive, only one half of CD3-immunoreactive tumors occurred in FeLV-positive cats. Median remission duration and survival times were 126 days and 143 days, respectively, for all cats. Measures of tumor cell proliferation (AgNOR frequency and PCNA-LI) and CD3-immunoreactivity were not predictive of outcome. When all prognostic factors were accounted for by multivariate analysis, response to therapy, FeLV status, and clinical substage were predictive of outcome. FeLV-negative cats that achieved a complete response following induction therapy were likely to have durable (ie, > 6-month) responses, particularly when doxorubicin was included in the chemotherapy protocol. However, FeLV-positive cats had significantly shorter remission and survival times with available chemotherapeutic protocols.