Treatment of cutaneous T‐cell lymphoma with dacarbazine in a dog

Background: Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5‐(3,3‐Dimethyl‐1‐triazeno)‐imidazole‐4‐carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma. Hypothesis: Single‐agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy. Animals: Forty client‐owned dogs with relapsed lymphoma. Methods: Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800–1,000 mg/m2 every 2–3 weeks as a 4–5‐hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed. Results: The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression‐free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7–14 days after the treatment. Treatments were delayed because of thrombocytopenia. Conclusions: DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma.

mentioning

confidence: 99%

Dacarbazine as Single‐Agent Therapy for Relapsed Lymphoma in Dogs

Griessmayr

Winter³

et al. 2009

“…There have been few controlled studies to evaluate the response of canine lymphoma to DTIC. A dog with cutaneous lymphoma and nodal involvement achieved a durable complete remission when treated with DTIC 13 . In 2 studies of dogs with relapsed lymphoma, complete and partial remissions were observed when DTIC was combined with doxorubicin 14,15 …”

mentioning

confidence: 99%

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

Flory

Rassnick

Al-Sarraf³

et al. 2008

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 5 .02). The principal toxic event was neutropenia; the median neutrophil count 7 days after treatment was 1,275 cells/mL. 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.

“…[5][6][7][8][9][10][11][12][13][14] Therapeutic approaches have been described in the veterinary literature but a standard of care therapy has not been established for canine ELSA. 5,[15][16][17][18] Reported response rates to retinoids, 16 cyclosporine, 18 fatty acids, 5 Lasparaginase, 6 dacarbazine, 15 and pegylated doxorubicin 7 generally are ,50% and are of short duration. A recent publication evaluating 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the treatment of ELSA by Williams et al 19 documented an overall response rate of 78%.…”

mentioning

confidence: 99%

Response of Canine Cutaneous Epitheliotropic Lymphoma to Lomustine (CCNU): A Retrospective Study of 46 Cases (1999–2004)

Risbon¹,

Lorimier

Skorupski

et al. 2006

Background: Epitheliotropic lymphoma (ELSA) is an uncommon cutaneous canine malignancy of T lymphocytes. A consensus regarding the therapeutic standard of care is lacking, warranting evaluation of chemotherapeutic agents traditionally employed against canine nodal lymphoma in the treatment of ELSA.Hypothesis: The purpose of this retrospective, multi-institutional study was to evaluate the efficacy of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the treatment of ELSA.Animals: Forty-six dogs with adequate follow-up and treatment response information. Methods: All cases were diagnosed histopathologically. Immunohistochemisty (CD3, CD79a) was performed on 42/46 samples.Results: Presenting skin lesions included generalized scales (25/46), plaques or nodules (22/46), mucocutaneous lesions (14/ 46), and corneal involvement (1/46). Lymph node involvement and Sézary syndrome were documented in 7 and 2 dogs, respectively. The median number of CCNU treatments was 4 (range, 1-11), with a median starting dose of 60 mg/m 2 (range, 30-95). Of the 46 dogs, 15 achieved complete remission, 23 achieved partial remission, 5 had stable disease, and 3 had progressive disease, for an overall response rate of 83%. The median number of treatments to achieve a response was 1 (range, 1-6). The overall median duration of response was 94 days (range, 22-282). Sixteen dose reductions were required because of neutropenia (10/46), thrombocytopenia (1/46), anemia (1/46), increased liver enzyme activity (3/46), or unspecified reasons (1/46).Conclusions and Clinical Implications: Given the high response rate and well tolerated protocol, prospective studies are warranted to investigate the utility of CCNU alone or in multi-agent protocols for the treatment of ELSA.