Combination of CCNU and DTIC Chemotherapy for Treatment of Resistant Lymphoma in Dogs

Flory, Andrea B.; Rassnick, Kenneth M.; Al-Sarraf, Renée; Bailey, Dennis B.; Balkman, Cheryl E.; Kiselow, Michael A.; Autio, Karoliina

doi:10.1111/j.1939-1676.2007.0005.x

Cited by 46 publications

(42 citation statements)

References 35 publications

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“…Previous studies have identified that the inclusion of multiple alkylating agents within chemotherapy protocols to treat canine multicentric lymphoma results in the T-cell phenotype no longer being a negative prognostic factor. 29,30 Mild toxicosis was fairly common with MOPP with 76% of the dogs experiencing at least 1 episode of hematologic toxicosis and 78% of the dogs experiencing at least 1 episode of gastrointestinal toxicosis. The most clinically relevant toxicosis was neutropenia, which was considered moderate to severe in 38% of the cases in which it was documented.…”

Section: Discussionmentioning

confidence: 99%

Asparaginase and MOPP Treatment of Dogs with Lymphoma

Brodsky¹,

Maudlin²,

Lachowicz³

et al. 2009

Veterinary Internal Medicne

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Background: Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success.Objectives: To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with L-asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP).Animals: Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals. Methods: Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement.Results: The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications.Conclusions and clinical importance: L-Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP.

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Section: Discussionmentioning

confidence: 99%

Asparaginase and MOPP Treatment of Dogs with Lymphoma

Brodsky¹,

Maudlin²,

Lachowicz³

et al. 2009

Veterinary Internal Medicne

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“…In a total of 72 previously reported cases, the mean age at the moment of diagnosis was 8. Evidences of renal toxicity, such as azotemia, polyuria, and polydipsia, are also reported, but usually to a lesser degree (HEADING et al, 2011;FLORY et al, 2008). In this study, although there were no complaints of clinical symptoms related to renal failure, increased values of urea (VCOG-CTCAE grade 1) and creatinine (VCOG-CTCAE grade 2) were observed in 66.6% (10/15) and 40% (6/15) ab Different letters in a row indicate significant difference (P Significant differences in serum levels of urea and urine density were observed between M1 and M2, thus suggesting the potential deleterious effects of the use of lomustine in the evaluated dogs (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Clinical and laboratorial evaluation of dogs with cutaneous lymphoma treated with lomustine

Duarte

Marques

Zahn

et al. 2016

Braz. J. Vet. Res. Anim. Sci.

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The aim of this prospective study was to evaluate the clinical response of dogs with cutaneous lymphoma treated with lomustine (CCNU) and to identify possible adverse effects and toxicity during treatment. Fifteen dogs, seven females and eight males aged between five and 17 years old, diagnosed with cutaneous lymphoma by histopathological analysis were selected and treated with lomustine at 90 mg/m² every three weeks. Monitoring was carried out and consisted of the assessment of laboratory hematology and serum chemistry before and during treatment. Partial response was observed in 53.3% of the animals. None of the animals achieved a complete response and seven dogs (46.6%) had progressive disease. The median survival time was 22 days. The major hematological and biochemical changes found after therapy were leukopenia (73.3%), thrombocytopenia (60%) and anemia (46.1%). Renal and liver toxicity was observed in 40% and 73.3% of dogs, respectively. Hematocrit, total protein, leukocyte count, neutrophil count, serum creatinine, ALT, GGT, alkaline phosphatase and urine specific gravity were affected during therapy. The use of lomustine as a monotherapy in the treatment of canine cutaneous lymphoma was effective; however, adverse effects occurred and compromised the quality of life of the majority of dogs in this study. Therefore, lower doses of lomustine should be considered in future studies. Keywords: CCNU. Cutaneous lymphoma. Dogs. Oncology. Adverse effects. ResumoO objetivo deste estudo prospectivo foi avaliar a resposta clínica de cães com linfoma cutâneo tratados com lomustina (CCNU) e identificar possíveis efeitos adversos e toxicidade durante o tratamento. Quinze cães, sendo 7 fêmeas e 8 machos, com idades entre 5 e 17 anos diagnosticados com linfoma cutâneo por avaliação histopatológica foram selecionados e tratados com lomustina na dose de 90 mg/m2 a cada três semanas. Os cães foram monitorados por avaliação hematológica e bioquímica sérica antes e durante o tratamento. A resposta parcial foi observada em 53,3% dos animais. Nenhum dos animais apresentou resposta completa e sete animais (46,6%) apresentaram progressão da doença. O tempo médio de sobrevida foi de 22 dias. As principais alterações hematológicas e bioquímicas observadas após o tratamento foram leucopenia (73,3%), trombocitopenia (60%) e anemia (46,1%). Sinais de toxicidade renal e hepática foram observados em 40% e 73,3% dos cães, respectivamente. Durante o tratamento foram afetados os parâmetros hematócrito, proteínas séricas totais, contagem de leucócitos, contagem de neutrófilos, creatinina sérica, ALT, GGT, fosfatase alcalina e densidade urinária. O uso de lomustina como monoterapia no tratamento do linfoma cutâneo canino foi efetivo; entretanto, efeitos adversos ocorreram e comprometeram a qualidade de vida da maioria dos animais neste estudo. Assim, sugere-se que doses mais baixas de lomustina sejam consideradas em estudos futuros.

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“…Median TTP for dogs achieving complete remission (CR) was 63 days versus a median TTP of 47 days in dogs achieving partial remission (PR). In 2008, Flory et al 9 reported an ORR of 35% in dogs with resistant lymphoma treated with the combination of lomustine and dacarabazine as a rescue protocol. Median TTP for dogs achieving CR was 83 days versus a median TTP of 25 days in dogs achieving PR.…”

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confidence: 99%

Combination Chemotherapy with Continuous l‐Asparaginase, Lomustine, and Prednisone for Relapsed Canine Lymphoma

Saba

Hafeman

Vail

et al. 2009

Veterinary Internal Medicne

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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.

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Combination of CCNU and DTIC Chemotherapy for Treatment of Resistant Lymphoma in Dogs

Cited by 46 publications

References 35 publications

Asparaginase and MOPP Treatment of Dogs with Lymphoma

Asparaginase and MOPP Treatment of Dogs with Lymphoma

Clinical and laboratorial evaluation of dogs with cutaneous lymphoma treated with lomustine

Combination Chemotherapy with Continuous l‐Asparaginase, Lomustine, and Prednisone for Relapsed Canine Lymphoma

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