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 μp = μL, (i.e. 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 weeks. A secondary endpoint, biologic observed response rate (BORR) was also calculated. Safety was assessed through the characterization and grading of adverse events (AE). Results: Overall CORR (7% versus 1%; P = 0.048) and BORR (23% versus 10%; P = 0.012) 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 due to hepatopathy compared to three (2%) receiving paclitaxel (micellar) (P < 0.0001; odds ratio 26.7). Conclusions/clinical importance: Paclitaxel (micellar)’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.
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 / Vail, D.; von Euler, H.; Rusk, A.; Barber, L.; Clifford, C.; Elmslie, R.; Fulton, L.; Hirschberger, J.; Klein, M. K.; London, C.; Martano, M.; Mcniel, E.; Morris, J.; Northrup, N.; Phillips, B.; Polton, G.; Post, G.; Rosenberg, M.; Ruslander, D.; Sahora, A.; Siegel, S.; Thamm, D.; Westberg, S.; Winter, J.; Khanna,. - In: JOURNAL OF VETERINARY INTERNAL MEDICINE. - ISSN 0891-6640. - 26:3(2012), pp. 598-607. [10.1111/j.1939-1676.2012.00897.x]
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
Martano M.;
2012-01-01
Abstract
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 μp = μL, (i.e. 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 weeks. A secondary endpoint, biologic observed response rate (BORR) was also calculated. Safety was assessed through the characterization and grading of adverse events (AE). Results: Overall CORR (7% versus 1%; P = 0.048) and BORR (23% versus 10%; P = 0.012) 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 due to hepatopathy compared to three (2%) receiving paclitaxel (micellar) (P < 0.0001; odds ratio 26.7). Conclusions/clinical importance: Paclitaxel (micellar)’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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
