Department of Medical Sciences, School of Veterinary Medicine and Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI 53706, USA.
J Vet Intern Med. 2012 May-Jun;26(3):598-607. doi: 10.1111/j.1939-1676.2012.00897.x. Epub 2012 Mar 6.
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 μ(p) = μ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively).
Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT.
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).
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).
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.
对于处于晚期的肥大细胞瘤（MCT）犬，仍迫切需要有效的治疗方法。紫杉醇胶束制剂（paclitaxel [micellar]）在早期研究中显示出良好的前景。
假设/目的：本研究旨在证明 paclitaxel [micellar] 比洛莫司汀更有效。零假设为μ(p) = μ(L)（即 paclitaxel [micellar] 和洛莫司汀组的应答比例分别为μ(p)和μ(L)）。
252 只患有晚期不可切除的 2 级或 3 级 MCT 的犬。
前瞻性多中心随机双盲阳性对照临床试验。主要终点是 14 周时的确认总缓解率（CORR）。还计算了生物学观察缓解率（BORR）这一次要终点。通过对不良事件（AE）的特征和分级来评估安全性。
与洛莫司汀相比，paclitaxel [micellar] 的总 CORR（7%对 1%；P =.048）和 BORR（23%对 10%；P =.012）更高。接受 paclitaxel [micellar] 治疗的犬更有可能出现确认缓解，且更有可能出现生物学观察缓解，其可能性分别是接受洛莫司汀治疗犬的 6.5 倍和 3.1 倍。paclitaxel [micellar] 相关的大多数 AE 是短暂的且临床可控的。与接受 paclitaxel [micellar] 治疗的 3 只犬（2%）相比，因肝毒性而停止接受洛莫司汀治疗的犬有 27 只（33%）（P <.0001；比值比 26.7）。
paclitaxel [micellar] 的疗效和安全性优于洛莫司汀。在兽医领域中增加一种有效的新型紫杉醇类药物可以满足很大的需求，而且由于其作用机制和 AE 谱与目前可用的 TKI 不重叠，其可用性可能会导致有效的联合治疗方案。
