Evaluation of 12-and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors

被引:60
作者
Hahn, Kevin A. [17 ]
Legendre, Alfred M. [1 ]
Shaw, Neil G. [2 ,3 ]
Phillips, Brenda [4 ]
Ogilvie, Gregory K. [5 ]
Prescott, Deborah M. [6 ]
Atwater, Stephen W. [7 ]
Carreras, Janet K. [8 ]
Lana, Susan E. [9 ]
Ladue, Tracy [10 ]
Rusk, Anthony [11 ]
Kinet, Jean Pierre [12 ,13 ]
Dubreuil, Patrice [14 ,15 ]
Moussy, Alain [15 ]
Hermine, Olivier [16 ]
机构
[1] Univ Tennessee, Coll Vet Med, Dept Small Anim Clin Sci, Knoxville, TN 37919 USA
[2] Florida Vet Specialists, Tampa, FL 33614 USA
[3] Canc Treatment Ctr, Tampa, FL 33614 USA
[4] Vet Specialty Hosp, San Diego, CA 92121 USA
[5] Calif Vet Specialists Angel Care Canc Ctr, Carlsbad, CA 92008 USA
[6] MedVet Associates Ltd, Worthington, OH 43085 USA
[7] E Bay Vet Specialists, Walnut Creek, CA 94598 USA
[8] Vet Canc Associates PA, Houston, TX 77027 USA
[9] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Clin Sci, Anim Canc Ctr, Ft Collins, CO 80523 USA
[10] SE Vet Oncol, Orange Pk, FL 32073 USA
[11] Friendship Hosp Anim, Washington, DC 20016 USA
[12] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[13] Harvard Univ, Sch Med, Boston, MA 02215 USA
[14] Ctr Rech Cancerol Marseille, INSERM, UMR 891, F-13009 Marseille, France
[15] AB Sci Soc Anonyme, F-75008 Paris, France
[16] Univ Paris 05, Hop Necker, CNRS, Serv Hematol,Ctr Reference Mastocytoses,UMR 8147, F-75015 Paris, France
[17] Gulf Coast Vet Specialists, Houston, TX 77027 USA
关键词
TYROSINE KINASE INHIBITOR; C-KIT; EXTRACELLULAR DOMAIN; END-POINTS; METASTASIS; MUTATIONS; CANCER; POTENT;
D O I
10.2460/ajvr.71.11.1354
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Objective-To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment. Animals-132 dogs with nonresectable grade 2 or 3 MCTs. Procedures-Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time. Results-In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib. Conclusions and Clinical Relevance-Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs. (Am J Vet Res 2010;71:1354-1361)
引用
收藏
页码:1354 / 1361
页数:8
相关论文
共 19 条
[1]  
[Anonymous], 2007, SURVIVAL ANAL PRACTI
[2]   We should desist using RECIST, at least in GIST [J].
Benjamin, Robert S. ;
Choi, Haesun ;
Macapinlac, Homer A. ;
Burgess, Michael A. ;
Patel, Shreyaskumar R. ;
Chen, Lei L. ;
Podoloff, Donald A. ;
Charnsangavej, Chuslip .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (13) :1760-1764
[3]   Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis [J].
Buyse, M ;
Thirion, P ;
Carlson, RW ;
Burzykowski, T ;
Molenberghs, G ;
Piedbois, P .
LANCET, 2000, 356 (9227) :373-378
[4]   Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT [J].
Dubreuil, Patrice ;
Letard, Sebastien ;
Ciufolini, Marco ;
Gros, Laurent ;
Humbert, Martine ;
Casteran, Nathalie ;
Borge, Laurence ;
Hajem, Berengere ;
Lermet, Anne ;
Sippl, Wolfgang ;
Voisset, Edwige ;
Arock, Michel ;
Auclair, Christian ;
Leventhal, Phillip S. ;
Mansfield, Colin D. ;
Moussy, Alain ;
Hermine, Olivier .
PLOS ONE, 2009, 4 (09)
[5]   Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis [J].
Ebos, John M. L. ;
Lee, Christina R. ;
Cruz-Munoz, William ;
Bjarnason, Georg A. ;
Christensen, James G. ;
Kerbel, Robert S. .
CANCER CELL, 2009, 15 (03) :232-239
[6]   Surrogate end points in clinical trials: Are we being misled? [J].
Fleming, TR ;
DeMets, DL .
ANNALS OF INTERNAL MEDICINE, 1996, 125 (07) :605-613
[7]   Masitinib is Safe and Effective for the Treatment of Canine Mast Cell Tumors [J].
Hahn, K. A. ;
Oglivie, G. ;
Rusk, T. ;
Devauchelle, P. ;
Leblanc, A. ;
Legendre, A. ;
Powers, B. ;
Leventhal, P. S. ;
Kinet, J. -P. ;
Palmerini, F. ;
Dubreuil, P. ;
Moussy, A. ;
Hermine, O. .
JOURNAL OF VETERINARY INTERNAL MEDICINE, 2008, 22 (06) :1301-1309
[8]   End points and United States food and drug administration approval of oncology drugs [J].
Johnson, JR ;
Williams, G ;
Pazdur, R .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (07) :1404-1411
[9]   Gain-of-function mutations in the extracellular domain of KIT are common in canine mast cell tumors [J].
Letard, Sebastien ;
Yang, Ying ;
Hanssens, Katia ;
Palmerini, Fabienne ;
Leventhal, Phillip S. ;
Guery, Stephanie ;
Moussy, Alain ;
Kinet, Jean-Pierre ;
Hermine, Olivier ;
Dubreuil, Patrice .
MOLECULAR CANCER RESEARCH, 2008, 6 (07) :1137-1145
[10]   Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours [J].
London, CA ;
Kisseberth, WC ;
Galli, SJ ;
Geissler, EN ;
Helfand, SC .
JOURNAL OF COMPARATIVE PATHOLOGY, 1996, 115 (04) :399-414