Dacarbazine as Single‐Agent Therapy for Relapsed Lymphoma in Dogs

Abstract

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.

Efficacy and toxicity of carboplatin and cytarabine chemotherapy for dogs with relapsed or refractory lymphoma (2000–2013)

“…Dogs receiving MOPP that had a response had a median time to progression of 60 days . Furthermore, dogs that received rescue chemotherapy with single‐agent DTIC that had a response had a median progression‐free interval of 43 days …”

Vinblastine as a second rescue for the treatment of canine multicentric lymphoma in 39 cases (2005 to 2014)

“…Numerous rescue protocols for dogs with relapsed or refractory lymphoma have been reported, including MOPP (mustargen, vincristine, procarbazine and prednisone) (Rassnick et al 2002 ), DMAC (dexamethasone, melphalan, actinomycin D and cyctosine arabinoside) (Alvarez et al 2006 ), MOMP (mechlorethamine, vincristine, melphalan and prednisone) (Back et al 2015 ), LOPP (lomustine, vincristine, procarbazine and prednisone) (Fahey et al 2011 ), ADIC (doxorubicin and dacarbazine) (Van Vechten et al 1990 ), single-agent DTIC (dacarbazine) (Griessmayr et al 2009 ) and CCNU (lomustine) +/− L-asparaginase (Moore et al 1999 ;Saba et al 2009 ) among many more. Secondary response rates, defined as the percentage of dogs achieving a complete or partial remission, vary from 35 to 77%.…”

Comparison of doxorubicin–cyclophosphamide with doxorubicin–dacarbazine for the adjuvant treatment of canine hemangiosarcoma

“…Dacarbazine is a non‐classical alkylating, phase non‐specific agent, which methylates the deoxyribonucleic acid (DNA) at the O 6 methyl group of guanine . Dacarbazine has previously been used in dogs for the treatment of relapsed or resistant lymphomas, high‐grade sarcomas and malignant melanomas, either as single agent or combined with lomustine or doxorubicin …”