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/m 2 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.

Background: The optimal dosage and clinical efficacy of vinblastine (VBL) for treatment of mast cell tumors (MCTs) in dogs has not been established.Hypothesis: Single-agent VBL has antitumor activity against MCTs in dogs. Animals: Fifty-one dogs with nonresectable grade II or III cutaneous MCTs. Methods:Prospective, open clinical trial. Dogs were systematically allocated (by hospital record number) to receive IV treatment with VBL at a dosage of 2.0 mg/m 2 (weekly for 4 treatments then biweekly for 4 treatments; VBL 2.0) or treatment with VBL at a dosage of 3.5 mg/m 2 (biweekly for 5 treatments; VBL 3.5). The primary outcome measure was reduction in tumor size.Results: Twenty-five dogs were allocated to the VBL 2.0 group and 26 were allocated to the VBL 3.5 group. In the VBL 2.0 group, 3 (12%) had a partial response (PR) for a median of 77 days (range, 48-229 days). Overall response rate in the VBL 3.5 group was 27%. One dog (4%) had a complete response for 63 days and 6 dogs (23%) had a PR for a median of 28 days (range, 28-78 days). Toxicoses were uncommon in the VBL 2.0 group. Twelve (46%) dogs in the VBL 3.5 group had o500 neutrophils/ mL 7 days after treatment; 2 dogs with neutropenia developed concurrent fevers.Conclusions and Clinical Importance: VBL, when used as a single-agent, has activity against MCTs in dogs although the response rate is lower than those reported for VBL-containing combination protocols. Further, findings suggest VBL at a dosage of 3.5 mg/m 2 should be considered for use in future phase II/III trials.

Safety and efficacy of a protocol of alternating 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; 70 mg m(-2)) and vinblastine (3.5 mg m(-2)), and prednisone (1-2 mg kg(-1); CVP) in dogs with mast cell tumours (MCT) were evaluated. A total of 17 dogs had nonresectable MCTs and 35 received CVP as adjunctive treatment to locoregional control of metastatic MCTs or grade III MCTs. Neutropenia with fever occurred in 8% of dogs after treatment with vinblastine and in 2% after treatment with CCNU. Persistent elevation of serum alanine transaminase, suggestive of hepatotoxicity, occurred in 9% of the dogs. Response rate in dogs with nonresectable MCTs was 65%; five achieved a complete response (median, 141 days) and six achieved a partial response (median, 66 days). Overall median progression-free survival (PFS) time in dogs treated in the adjuvant setting was 489 days. Dogs with grade III MCTs had shorter PFS compared with dogs with metastatic grade II MCTs (190 days versus 954 days; P < 0.001). Phase III studies are needed to provide reliable information about the comparative efficacy of this protocol.