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.

Consolidation with either CCNU/MOPP or HBRT showed no advantage over a standard CHOP-based protocol.

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.