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

作者：Vail D M^*; von Euler H; Rusk A W; Barber L; Clifford C; Elmslie R; Fulton L; Hirschberger J; Klein M; London C; Martano M; McNiel E A; Morris J S; Northrup N; Phillips B; Polton G; Post G; Rosenberg M; Ruslander D; Sahora A; Siegel S; Thamm D; Westberg S; Winter J; Khanna C

来源：Journal of Veterinary Internal Medicine, 2012, 26(3): 598-607.

DOI：10.1111/j.1939-1676.2012.00897.x

• Cancer
• Canine
• Chemotherapy
• Paclitaxel
• Taxane

Background Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies. Hypothesis/Objectives The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was mu p similar to mu L (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively). Animals Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT. Methods Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 similar to weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE). Results Overall CORR (7% versus 1%; P similar to 048) and BORR (23% versus 10%; P similar to 012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P similar to 0001; odds ratio 26.7). Conclusions and Clinical Importance Paclitaxel (micellar)%26apos;s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.

• 出版日期2012-6