title: 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.
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.
  
  
  OBJECTIVE
  The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was μ(p) = μ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively).
  
  
  METHODS
  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), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE).
  
  
  RESULTS
  Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .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 < .0001; odds ratio 26.7).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine and Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI 53706, USA. vaild@svm.vetmed.wisc.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
authors.forename: H
authors.initials: H
authors.lastname: von Euler
authors.forename: A W
authors.initials: AW
authors.lastname: Rusk
authors.forename: L
authors.initials: L
authors.lastname: Barber
authors.forename: C
authors.initials: C
authors.lastname: Clifford
authors.forename: R
authors.initials: R
authors.lastname: Elmslie
authors.forename: L
authors.initials: L
authors.lastname: Fulton
authors.forename: J
authors.initials: J
authors.lastname: Hirschberger
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.forename: C
authors.initials: C
authors.lastname: London
authors.forename: M
authors.initials: M
authors.lastname: Martano
authors.forename: E A
authors.initials: EA
authors.lastname: McNiel
authors.forename: J S
authors.initials: JS
authors.lastname: Morris
authors.forename: N
authors.initials: N
authors.lastname: Northrup
authors.forename: B
authors.initials: B
authors.lastname: Phillips
authors.forename: G
authors.initials: G
authors.lastname: Polton
authors.forename: G
authors.initials: G
authors.lastname: Post
authors.forename: M
authors.initials: M
authors.lastname: Rosenberg
authors.forename: D
authors.initials: D
authors.lastname: Ruslander
authors.forename: A
authors.initials: A
authors.lastname: Sahora
authors.forename: S
authors.initials: S
authors.lastname: Siegel
authors.forename: D
authors.initials: D
authors.lastname: Thamm
authors.forename: S
authors.initials: S
authors.lastname: Westberg
authors.forename: J
authors.initials: J
authors.lastname: Winter
authors.forename: C
authors.initials: C
authors.lastname: Khanna
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004311:Double-Blind Method; D005260:Female; D008297:Male; D012515:Mast-Cell Sarcoma / Q000188:drug therapy / Q000662:veterinary*; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000627:therapeutic use*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D017239:Paclitaxel