A phase II study to evaluate the toxicity and efficacy of alternating CCNU and high-dose vinblastine and prednisone (CVP) for treatment of dogs with high-grade, metastatic or nonresectable mast cell tumours

Abstract

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.

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

“…The incidence and severity of increased ALT activity was less than previously reported, which may be due in part to early intervention with hepatoprotectants, dose delays, or both when mild increases in ALT activity developed. The maximally tolerated dosage of lomustine in this protocol was 50 mg/m 2 , which is 28.6–44% lower than lomustine dosages reported elsewhere for treatment of MCT . This decreased lomustine dosage also may have decreased the frequency and severity of hepatotoxicity observed in this study as compared to previous studies.…”

“…Therapeutic challenges, however, arise with MCT that are large or infiltrative, high grade, have metastasized beyond the regional lymph node, or are located where wide surgical excision is not possible. Several medical treatments have been studied for MCT in dogs, including corticosteroids alone, lomustine, chlorambucil, hydroxyurea, and vinblastine as well as various combinations of these agents . Although generally well tolerated, response rates frequently remain at or below 50% and usually are brief and incomplete …”

A Randomized Trial Investigating the Efficacy and Safety of Water Soluble Micellar Paclitaxel (Paccal Vet) for Treatment of Nonresectable Grade 2 or 3 Mast Cell Tumors in Dogs

“…The dosage of paclitaxel (micellar) had been established from previous studies . Lomustine was chosen as the positive control because other appropriate veterinary‐registered treatments were not available when the study was initiated, anecdotal activity of lomustine in canine MCT was documented in the veterinary literature, and its 3‐week treatment cycle was consistent with 3‐week intervals used with paclitaxel (micellar). The rationale for and dose of lomustine were adopted from the literature and consultation with key opinion leaders in veterinary oncology …”

“…The current practice of veterinary oncology relies, for the most part, on the extra‐label use of chemotherapeutics registered for use in humans. The 2 most commonly used cytotoxic agents currently thought to have activity against canine MCT disease are lomustine and vinblastine . These agents have not been subject to rigorous GCP‐standard field trials and their safety and activity in companion dogs therefore is considered to be anecdotal.…”

Canine mast cell tumours: decision‐making and treatment

“…Vinblastine, in combination with prednisolone, has been shown to be beneficial in increasing survival time over historical controls in the management of high-grade MCTs (two year disease-free interval 70 per cent) (Hayes and others 2007), and grade 2 to 3 MCTs with a high risk of metastasis (MST of 1305 days) (Thamm and others 2006). The addition of lomustine (CCNU) to the combination of vinblastine and prednisolone has also shown favourable outcomes in grade 3 or metastatic MCTs, with a median progression-free survival (PFS) of 489 days (Rassnick and others 2010). A further study adding cyclophosphamide to the vinblastine and prednisolone led to a median PFS of 865 days (Camps-Palau and others 2007).…”